Inhibition and dispersion of biofilms in plants with imidazole-triazole derivatives

ABSTRACT

Disclosure is provided for methods of preventing, removing or inhibiting microbial biofilm formation or microbial infection in a plant or plant part thereof, including applying thereto a treatment effective amount of an active compound as described herein, or an agriculturally acceptable salt thereof. Methods of enhancing a microbicide (e.g., including a copper, antibiotic, bacteriophage, etc.) and/or plant defense activator are also provided, including applying an active compound as described herein. Compositions comprising an active compound as described herein in an agriculturally acceptable carrier are also provided, and in some embodiments the compositions further include a microbicide (e.g., including copper, antibiotic, bacteriophage, etc.) and/or plant defense activator.

RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. §119(e) of U.S.Application No. 61/120,661, filed Dec. 8, 2008 the disclosure of whichis incorporated herein by reference in its entirety. This application isrelated to U.S. application Ser. No. 12/426,742, filed Apr. 20, 2009,and published Oct. 22, 2009, as publication no. 2009/0263438, thedisclosure of which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

This invention relates to compositions and methods useful forcontrolling biofilms and microorganisms in plants, particularly vascularplants.

BACKGROUND OF THE INVENTION

New approaches are urgently needed to improve agricultural production,given the steadily growing global population that is predicted to reach6-9 billion persons by mid-century, the continual strain on existing andfinite agricultural lands, and the recent diversion of valuableagricultural land from production of crops to production of biomass forfuels. Here we describe new approaches to increase agriculturalproduction by controlling the adverse effects of microorganisms onplants.

The five main crops on which modern societies depend most heavilyinclude corn, cotton, rice, soybeans, and wheat. All of these crops areaffected in a deleterious manner by biofilm formation. In addition,other valuable plants such as those producing fruits and vegetables aresimilarly affected. Plants grown for biomass stand to increase as avaluable crop, albeit not for food, and also can benefit from protectionfrom biofilm formation. Forestry crops and ornamentals also suffer frombiofilms.

SUMMARY OF THE INVENTION

The present invention is a method of preventing, removing or inhibitingmicrobial biofilm formation or microbial infection in a plant or plantpart thereof, comprising applying to the plant or plant part a treatmenteffective amount of a compound selected from the group consisting ofcompounds of Formula (I), Formula (I)(a)(1), Formula (I)(b)(1), Formula(I)(a)(2), Formula (I)(b)(2), Formula (I)(i), Formula (I)(i)(a), Formula(II), Formula (II)(a), Formula (II)(i), Formula (II)(i)(a), Formula(III), Formula (III)(a), Formula (III)(b), Formula (III)(b)(i), Formula(III)(b)(ii), Formula (IV), Formula (IV)(a), Formula (IV)(i), Formula(IV)(i)(a), Formula (V), Formula (V)(a), Formula (V)(i), Formula(V)(i)(a), Formula (VI), Formula (VI)(a), Formula (VI)(i) and Formula(VI)(i)(a) as described herein, or an agriculturally acceptable saltthereof.

In some embodiments, the plant is a fruit or a vegetable crop plant.

In some embodiments, the plant is a citrus tree, and the compound isapplied in an amount effective to treat or control a bacterial diseaseselected from the group consisting of canker, bacterial spot, Black Pit(fruit), Blast, citrus variegated chlorosis, and Citrus Huanglongbing.In some embodiments, the citrus tree is selected from the groupconsisting of orange, grapefruit, Mandarin, lemon, lime and Kumquat.

In some embodiments, the plant is a pome fruit, and the compound isapplied in an amount effective to treat or control a bacterial diseaseselected from the group consisting of Fire Blight, Crown Gall, Blisterspot and Hairy root. In some embodiments, the pome fruit is selectedfrom the group consisting of apple, pear, quince, Asian pear, andloquats.

In some embodiments, the plant is a Musa species such as a banana, andthe compound is applied in an amount effective to treat or controlRalstonia solanacearum.

In some embodiments, the plant is a cole (Brassicaceae) such as cabbageor broccoli, and the compound is applied in an amount effective to treator control black rot (Xanthomonas campestris).

In some embodiments, the plant is a winegrape, and the compound isapplied in an amount effective to treat or control for Pierce's disease(Xylella fastidosa) or crown gall (Agrobacterium vitas, A.tutnefaciens).

In some embodiments, the plant is a stone fruit or nut (e.g., peaches,nectarines, plums, almonds, walnuts), and the compound is applied in anamount effective to treat or control bacterial spot and/or blight causedby Xanthomonas arboricola; blight caused by Pseudomonas syringae); crowngall caused by Agrobacterium tumefaciens; phony peach and plum; oralmond leaf scorch caused by Xylella fastidosa.

In some embodiments, the plant is a landscape and/or shade tree (e.g.,oak, maple, birch, etc.) for bacterial leaf scorch disease (e.g., causeby Xylella fastidosa).

In some embodiments, the plant is a potato, and the compound is appliedin an amount effective to treat or control soft rot or black leg(Erwinia, Pectobacterium).

In some embodiments, the plant is a pepper plant, and the compound isapplied in an amount effective to treat or control a bacterial diseaseselected from the group consisting of Bacterial Spot, Bacterial wilt,Bacterial canker, and Syringae seedling blight and leaf spot.

In some embodiments, the plant is a tomato plant, and the compound isapplied in an amount effective to treat or control a bacterial diseaseselected from the group consisting of: bacterial canker, bacterialspeck, bacterial spot, bacterial stern rot and fruit rot, Bacterialwilt, Pith necrosis, and Syringae leaf spot.

In some embodiments, the plant is a soybean plant, and the compound isapplied in an amount effective to treat or control a bacterial diseaseselected from the group consisting of Bacterial blight, Bacterialpustules, Bacterial wilt, Bacterial crinkle leaf, Bacterial tan spot,and Wildfire.

In some embodiments, the plant is corn, and the compound is applied inan amount effective to treat or control a bacterial disease selectedfrom the group consisting of: Bacterial leaf blight, stalk rot,bacterial stripe, chocolate spot, holcus spot all causes by Pseudomonasspecies, Bacterial leaf spot caused by Xanthomonas species, Bacterialstalk rot, top rot and Stewart's disease caused by Erwinia species, seedrot-seedling blight caused by Bacillus species, Purple leaf sheathcaused by Heimparctsitic bacteria, Corn stunt caused by Spriroplastitakunkelii, Goss's bacterial wilt and blight caused by Clivibactermichigcmensis.

In some embodiments, the plant is cotton, and the compound is applied inan amount effective to treat or control a bacterial disease selectedfrom the group consisting of Bacterial blight caused by Xanthomonasspecies, and Crown gall caused by Agrobacterium species and Lintdegradation caused by Erwinia species.

In some embodiments, the plant is wheat, and the compound is applied inan amount effective to treat or control a bacterial disease selectedfrom the group consisting of Bacterial leaf blight, bacterial sheath rotand Basal glume rot caused by Pseudomonas species, Bacterial mosaic andSpike blight caused by Clavibacter species, Black chaff caused byXanthomonas species, and Pink seed caused by Erwinia (Pantoea) species.

In some embodiments, the plant is rice, and the compound is applied inan amount effective to treat or control a bacterial disease selectedfrom the group consisting of bacterial blight and leaf streak caused byXanthomonas species, Foot rot caused by Erwinia species, Grain rotcaused by Burkholderia species, and Sheath brown rot caused byPseudomonas species.

In some embodiments, the plant is pineapple, and the compound is appliedin an amount effective to treat or control a bacterial disease selectedfrom the group consisting of bacterial heart rot, fruit collapse,bacterial fruitlet brown rot, marbled fruit, pink fruit and soft rotcaused by Erwinia species, and Acetic souring caused by Acetic acidbacteria.

In some embodiments, the microbial biofilm formation or microbialinfection is caused by a fungi. In some embodiments, the compound isapplied to the plant in an amount effective to treat or control a fungaldisease selected from the group consisting of rots, leaf molds, blights,wilts, damping-off, spot, root rot, stem rot, mildew, brown spot,gummosis, melanose, post-bloom fruit drop, scab, alternaria, canker,flyspeck, fruit blotch, dieback, downy mildews, ear rots, anthracnosebunts, smut, rust, eyespot and pecky rice.

In some embodiments, the plant is citrus, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Alternaria brown spot caused by Alternariaalternaria, Brown rot caused by Phytophtora citricola, Greasy spot andGreasy spot rind blotch caused by Mycosphaerella citri, Melanose causedby Diaporthe citri, Phytophthora foot rot, gummosis and root rot causedby Phytophthora citrophthora, Phytophthora palmivora, Phytophthorasyringae and other Phytophthora spp, Post bloom fruit drop caused byColletotrichum acutatum, and Scab caused by Elsinoe fawcettii.

In some embodiments, the plant is Pome fruit, and the compound isapplied in an amount effective to treat or control a fungal diseaseselected from the group consisting of: Apple scab caused by Venturiainaequalis, Bitter rot caused by Colletotrichum gloeosporioides,Diplodia canker caused by Dilpodia mutila, Phytophthora crown, collar,root and fruit rot caused by Phytophthora spp., Powdery mildew caused byPodosphaera leucotricha, Pacific Coast pear rust, Cedar apple rust,Quince rust caused by Gymnosporangiwn spp., and Flyspeck caused bySchizothyrium pomi.

In some embodiments, the plant is Peppers, and the compound is appliedin an amount effective to treat or control a fungal disease selectedfrom the group consisting of: Anthracnose caused by Colletotrichum spp.,Damping-off and root rot caused by Rhizoctonia solani, Phytophthoraspp., Fusarium spp., and Pythium spp., Phytophthora blight caused byPhytophthora capsici, and Verticillium wilt caused by Verticilliumalbo-atrium.

In some embodiments, the plant is Tomato, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Alternaria stem canker caused by Alternariaalternaria, Anthracnose caused by Colletotrichum spp., Fusarium crown,root rot and wilt caused by Fusarium oxysporum, Gray mold caused byBotrytis cinerea, Late blight caused by phytophthora infestans, Pythiumdamping-off and fruit rot caused by Pythium spp., Rhizoctoniadamping-off and fruit rot caused by Rhizoctonia solani, Septoria leafspot caused by Septoria lycopersici, Verticillium wilt caused byVerticillium albo-atrum, and White mold caused by Sclerotiniasclerotiorwn.

In some embodiments, the plant is Soybean, and the compound is appliedin an amount effective to treat or control a fungal disease selectedfrom the group consisting of: Phytophthora root and stem rot caused byPhytophthora sojae, Pythium root rot, damping-off and seed decay causedby Pythium spp., Brown stern rot caused by Phialophora gregata,Rhizoctonia root and stem rot caused by Rhizoctonia solani, Sterncanker, pod and stem blight caused by Diaporthe phaseolorum, Phomopsisseed decay caused by Phomopsis longicolla, Charcoal rot caused byMacrophomina phaseolina, Sclerotinia stem rot caused by Sclerotiniasclerotiorum, Sudden death syndrome caused by Fusarium solani, andSoybean Rust caused by Phakopsora pachyrhizi.

In some embodiments, the plant is Grape, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Alternaria rot caused by Alternaria alternaria,Angular leaf spot caused by Mycosphaerella angulata, Botrytis bunch rotand blight caused by Botrytis cinerea, Diplodia cane dieback and bunchrot caused by Diplodia natalensis, Downy mildew caused by Plasmoparaviticola, Phytophthora crown and root rot caused by Phytophthora spp.,Powdery mildew caused by Uncinula necator, Ripe rot caused by Glomerellacingulata, Septoria leaf spot caused by Septoria ampelopsidis, andVerticillium wilt caused by Verticillium dahliae.

In some embodiments, the plant is Potato, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Brown spot, Black pit and Early blight causedby Alternaria spp., Fusarium dry rot and wilt caused by Fusarium spp.,Gangrene caused by Phoma spp., Late blight and Pink rot caused byPhytophthora spp., Rhizoctonia canker and black scurf caused byRhizoctonia solani, Rosellinia black rot caused by Rosellinia spp.,Septoria leaf spot caused by Septoria lycopersici, Stem rot caused bySclerotium rolfsii, Verticillium wilt caused by Verticillium albo-atrum,and White mold caused by Sclerotinia sclerotiorum.

In some embodiments, the plant is Pineapple, and the compound is appliedin an amount effective to treat or control a fungal disease selectedfrom the group consisting of: Anthracnose caused by Colletotrichumananas, Bull rot and White leaf spot caused by Chalara paradoxa, Leafspot caused by Curvularia eragrostidis, Phytophthora heart rot caused byPhytophthora cinnamomi and Phytophthora parasitica, Root rot andSeedling blight caused by Pythium spp., and Leaking brown ring caused byTofflieadis dimenationa.

In some embodiments, the plant is Cotton, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Anthracnose caused by Glomerella gossypii, Bollrot caused by Colletotrichum gossypii, Fusarium spp., Phytophthora spp.,or Rhizoctonia solani, Fusarium wilt caused by Fusarium oxysporum, Leafspot caused by Alternaria spp., Cercospora gossypina, Rhizoctoniasolani, and Stemphylium solani, Lint contamination caused by Aspergillusflavus, Powdery mildew caused by Leveillula taurica, Cotton rust causedby Puccinia schedonnardii, Southwestern cotton rust caused by Pucciniacacabata, Tropical cotton rust caused by Phakopsora gossypii, Southernblight caused by Sclerotium rolfsii, Seedling disease complex caused byColletotrichum gossypii, Fusarium spp., Pythium spp., Rhizoctoniasolani, or Thielaviopsis basicola, Stem canker caused by Phoma exigua,and Verticillium wilt caused by Verticillium dahliae.

In some embodiments, the plant is Corn, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Anthracnose caused by Colletotrichumgraminicola, Aspergillus ear and kernel rot caused by Aspergillusflavus, Banded leaf, sheath spot, root rot and stalk rot caused byRhizoctonia solani, Brown spot, Black spot and Stalk rot caused byPhysoderma maydis, Curvularia leaf spot caused by Curvularia clavata,Diplodia ear rot, stalk rot, seed rot and seedling blight caused byDilpodia spp., Downey mildews caused by Sclerophthora spp. orPeronosclerospora spp., Ear rots caused by Alternaria alternaria, Ergotcaused by Claviceps gigantea, Fusarium ear, stalk, kernel, root, seedrot, seedling blight caused by Fusarium spp., Cercospora leaf spotcaused by Cercospora zeae-maydis, Helminthosporium ear rot caused byHelminthosporium carbonum, Pythium root rot and stalk rot caused byPythium spp., Rhizoctonia ear rot caused by Rhizoctonia zeae, Commoncorn rust and Southern corn rust caused by Puccinia spp., Southernblight caused by Athelia rolfsii, Common smut caused by Ustilago zeae,Southern corn leaf blight and stalk rot caused by Cochliobolusheterostrophus, and storage rots caused by Aspergillus spp. andPenicillium spp.

In some embodiments, the plant is Rice, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Black kernel caused by Curvularia lunata, Blastcaused by Pyricularia oryzae, Brown spot caused by Cochliobolusmiyabeanus, Downy mildew caused by Sclerophthora macrospora, False smutcaused by Ustilaginoidea Wrens, Narrow brown leaf spot caused byCercospora janseana, Pecky rice caused by Fusarium spp., Microdochiumoryzae, or Sarocladium oryzae, Root rot caused by Fusarium spp, orPythium spp., Seedling blight caused by fungi (e.g., Cochliobolusmiyabeanus, Curvularia spp., Fusarium spp., Rhizoctonia solani,Sclerotium rolfsii and Athelia Stackburn caused by Alternaria padwickii,Stem rot caused by Magnaporthe salvinii, Water-mold (seed-rot andseedling disease) caused by Achlya spp., Fusarium spp., or Pythium spp.

In some embodiments, the plant is Wheat, and the compound is applied inan amount effective to treat or control a fungal disease selected fromthe group consisting of: Alternaria leaf blight caused by Alternariatriticina, Anthracnose caused by Colletotrichum graminicola, Black headmolds caused by Cladosporium spp., Epicoccum spp., Sporobolomyces spp.or Stemphylium spp., Common bunt caused by Tilletia spp., Crown rot,seedling blight and dryland root rot caused by Fusarium spp. orGibberella spp., Downey mildew caused by Sclerophthora macrospora, Dwarfbunt caused by Tilletia controversa, Ergot caused by Claviceps putpurea,Eyespot caused by Tapesia yallundae, Leaf rust caused by Pucciniatriticina, Loose smut caused by Ustilago tritici, Microscopia leaf spotcaused by Phaeosphaeria microscopia, Phoma spot caused by Phoma spp.,Powdery mildew caused by Erysiphe graminis, Pythium root rot, Snow rotcaused by Pythium spp., Rhizoctonia root rot caused by Rhizoctoniasolani, Scab (head blight) caused by Fusarium spp. or Gibberella spp.,Southern blight caused by Sclerotium Speckled snow mold caused byTyphula spp., Stem rust caused by Puccinia graminis, storage moldscaused by Aspergillus spp. or Penicillium spp., Take-all caused byGaeumannomyces graminis, and Zoosporic root rot caused by Lagenaradicola.

A further aspect of the present invention is an agricultural compositioncomprising: (a) an agriculturally acceptable carrier (e.g., an aqueouscarrier or a solid particulate carrier); and (b) an antimicrobial orbiofilm preventing, removing or inhibiting compound selected from thegroup consisting of compounds of Formula (I), Formula (I)(a)(1), Formula(I)(b)(1), Formula (I)(a)(2), Formula (I)(b)(2), Formula (I)(i), Formula(I)(i)(a), Formula (II), Formula (II)(a), Formula (II)(i), Formula(II)(i)(a), Formula (III), Formula (III)(a), Formula (III)(b), Formula(III)(b)(i), Formula (III)(b)(ii), Formula (IV), Formula (IV)(a),Formula (IV)(i), Formula (IV)(i)(a), Formula (V), Formula (V)(a),Formula (V)(i), Formula (V)(i)(a), Formula (VI), Formula (VI)(a),Formula (VI)(i) and Formula (VI)(i)(a) as described herein, or anagriculturally acceptable salt thereof. In some embodiments, thecomposition further includes a microbicide. In some embodiments, themicrobicide comprises copper (e.g., copper hydroxide). In someembodiments, the microbicide comprises an antibiotic or a bacteriophage.In some embodiments, the composition further includes a plant defenseactivator. In some embodiments, the composition further includes both aplant defense activator and a microbicide.

In some embodiments, the compound is a compound of Formula(II)(a)(5)(D):

or an agriculturally acceptable salt thereof.

Further provided are methods of enhancing the effects of a microbicidecomprising applying an active compound selected from the groupconsisting of compounds of Formula (I), Formula (I)(a)(1), Formula(I)(b)(1), Formula (I)(a)(2), Formula (I)(b)(2), Formula (I)(i), Formula(I)(i)(a), Formula (II), Formula (II)(a), Formula (II)(i), Formula(II)(i)(a), Formula (III), Formula (III)(a), Formula (III)(b), Formula(III)(b)(i), Formula (III)(b)(ii), Formula (IV), Formula (IV)(a),Formula (IV)(i), Formula (IV)(i)(a), Formula (V), Formula (V)(a),Formula (V)(i), Formula (V)(i)(a), Formula (VI), Formula (VI)(a),Formula (VI)(i) and Formula (VI)(i)(a) as described herein, incombination with said microbicide. In some embodiments, the microbicidecomprises copper (e.g., copper hydroxide). In some embodiments, themicrobicide is an antibiotic or a bacteriophage. In some embodiments,the applying step is carried out by applying the active compound and themicrobicide simultaneously. In some embodiments, the applying step iscarried out by applying the active compound and the microbicidesequentially. In some embodiments, the compound is a compound of Formula(II)(a)(5)(D):

or an agriculturally acceptable salt thereof.

Also provided are methods of enhancing the effects of a plant defenseactivator comprising applying an active compound selected from the groupconsisting of compounds of Formula (I), Formula (I)(a)(1), Formula(I)(b)(1), Formula (I)(a)(2), Formula (I)(b)(2), Formula (I)(i), Formula(I)(i)(a), Formula (II), Formula (II)(a), Formula (II)(i), Formula(II)(i)(a), Formula (III), Formula (III)(a), Formula (III)(b), Formula(III)(b)(i), Formula (III)(b)(ii), Formula (IV), Formula (IV)(a),Formula (IV)(i), Formula (IV)(i)(a), Formula (V), Formula (V)(a),Formula (V)(i), Formula (V)(i)(a), Formula (VI), Formula (VI)(a),Formula (VI)(i) and Formula (VI)(i)(a) as described herein, incombination with said plant defense activator. In some embodiments, theapplying step is carried out by applying the active compound and themicrobicide simultaneously. In some embodiments, the applying step iscarried out by applying the active compound and the microbicidesequentially. In some embodiments, the compound is a compound of Formula(II)(a)(5)(D):

or an agriculturally acceptable salt thereof.

A further aspect of the present invention is an antimicrobial or biofilmpreventing, removing or inhibiting compound selected from the groupconsisting, of compounds of Formula (I), Formula (I)(a)(1), Formula(I)(b)(1), Formula (I)(a)(2), Formula (I)(b)(2), Formula (I)(i), Formula(I)(i)(a), Formula (II), Formula (II)(a), Formula (II)(i), Formula(II)(i)(a), Formula (III), Formula (III)(a), Formula (III)(b), Formula(III)(b)(i), Formula (III)(b)(ii), Formula (IV), Formula (IV)(a),Formula (IV)(i), Formula (IV)(i)(a), Formula (V), Formula (V)(a),Formula (V)(i), Formula (V)(i)(a), Formula (VI), Formula (VI)(a),Formula (VI)(i) and Formula (VI)(i)(a) as described herein, for use intreating or preventing a bacterial or fungal infection in a plant orplant part as described above and below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Construction of the initial 2-AIT library.

FIG. 2. Variation on tether length.

FIG. 3. Effects of bacterial spot disease on pepper plants and crops.

FIG. 4. Evaluation of foliar disease on inoculated pepper plants.

FIG. 5. Pepper fruit yield per inoculated plant.

FIG. 6. Evaluation of foliar disease on pepper plants measured by plotaverage.

FIG. 7. Average pepper fruit yield per plant/plot, July 1 and 9harvests.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is further described below. All patent referencesreferred to in this patent application are hereby incorporated byreference in their entirety as if set forth fully herein.

A. Definitions.

“Active compound” as used herein refers to the various embodiments ofcompounds described in Section B (triazole derivatives) set forth below.

“Plant” as used herein includes all members of the plant kingdom,including higher (or “vascular”) plants and lower (“non-vascular”)plants, and particularly including all plants in the divisionsFilicinae, Gymnospermae (or “gymnosperm”), and Angiospermae (or“Angiosperm”). Nonvascular plants of the present invention include, butare not limited to, bryophytes.

A plant of the present invention includes, but is not limited to, a cropplant, a turf grass, an ornamental species, a species grown for timberor pulp, a species grown for biofuels or species grown forpharmaceuticals. Additionally, plants of the present invention include,but are not limited to, tobacco, tomato, potato, sugar beet, pea,carrot, cauliflower, broccoli, soybean, canola, sunflower, alfalfa,cotton, rapeseed, Arabidopsis, peach, pepper, apple, chile, peanut,orange, grape, coffee, cassava, spinach, lettuce, cucumber, wheat,maize, rye, rice, turfgrass, oat, barley, sorghum, millet, sugarcane, orbanana.

“Angiosperm” as used herein includes, but is not limited to, plants ofthe sub-classes Monocotyledoneae (or monocots) and Dicotyledoneae (ordicots).

Monocotyledoneae (or monocots) as used herein includes but is notlimited to Amaryllidaceae—the Amaryllis Family, Gramineae(Poaceae)—theGrass Family, Liliaceae—the Lily Family, Orchidaceae—the Orchid Family,Palmae(Aracaceae)—the Palm Family; and Lemnacea—the duckweed family.

Dicotyledoneae (or dicots) as used herein includes but is not limited toCactacae—the Cactus Family, Compositae (Asteraceae)—the SunflowerFamily, Cruciferae (Brassicaceae)—the Mustard Family, Cucurbitaceae—theGourd Family, Ericaceae—the Heath Family, Euphorbiaceae—the SpurgeFamily, Lauraceae—the Laurel Family, Leguminosae (Fabaceae)—the PeaFamily, Rosaceae—the Rose Family, Rutaceae—the Rue Family,Solanaceae—the Nightshade Family, and Umbelliferae (Apiaceae)—the Carrotfamily.

Gymnospermae (or “Gymnosperms”) as used herein includes but is notlimited to conifers.

“Conifer,” as used herein, refers to a member of the order Coniferae inthe sub-phylum Gymnospermae in the phylum Spermaphyta. Exemplaryconifers which may be used in practicing the present invention are themembers of the family Pinaceae, which include, for example, loblollypine (Pinus taeda), slash pine (Pinus elliotii), longleaf pine (Pinuspalustris), shortleaf pine (Pinus echinata), ponderosa pine (Pinusponderosa), red pine (Pinus resinosa), jack pine (Pinus banksiana),Eastern white pine (Pinus strobus), Western white pine (Pinusmonticola), sugar pine (Pinus lambertiana), Iodgepole pine (Pinuscontorta), Monterey pine (Pinus radiata), Afghan pine (Pinus eldarica),Scots pine (Pinus sylvestris), and Virginia pine (Pinus virdniana);Douglas-fir (Pseudotsuga menziesii); Western hemlock (Tsuga canadensis);Sitka spruce (Picea glauca); redwood (Sequoia sempervirens); the truefirs including silver fir (Abies amabilis), grand fir (Abies grandis)noble fir (Abies procera), white fir (Abies concolor), balsam fir (Abiesbalsamea); and the cedars which include Western red cedar (Thujaplicata), incense cedar (Libocedrus decurrens), Port Orford cedar(Chamaecyparis lawsoniona), and Alaska yellow-cedar (Chamaecyparisnootkatensis); and Western larch (Laryx occidentalis). See, e.g., U.S.Pat. No. 5,122,466 to Stomp et al.

“Duckweed” as used herein includes plants of the genus Lemna (L.aequinoctialis, L. dispenna, L. ecuadoriensis, L. gibba, L. japonica, L.minor, L. miniscula, L. obscura, L. perpusilla, L. tenera, L. trisulca,L. turionifera, L. valdivian); genus Spirodela (S. intermedia, S.polyrrhiza, S. punctata); genus Wolffia (Wa. angusta, Wa. arrhiza, Wa.australina, Wa. borealis, Wa. brasiliensis, Wa. columbiana, Wa.elongata, Wa. globosa, Wa. microscopica, Wa. neglecta) and genusWolfiella (WI. caudata, WI. denticulata, WI. gladiata, WI. hyalina, WI.lingulata, WI. repunda, WI. rotunda, and WI. neotropica). See, e.g.,U.S. Pat. No. 7,161,064 to Stomp et al.

Particular examples of plants include but are not limited to all cerealand grain crops, herbs and spices, oil seed crops, sugarcane, vegetablecrops, brassica vegetables, bulb vegetables, cucurbit vegetables andfruit, leafy vegetables, fruiting vegetables, legume vegetables, rootand tuber vegetables, tree, vine and shrub crops, berry crops, citrus(e.g., orange, grapefruit, Mandarin (including Tangerine and Satsuma),lemon, lime, and kumquat), pome fruit (e.g., apple, pear, quince, Asianpear, loquat, etc.), stone fruit (e.g., peach, apricot, prune, plum,cherries, almond, etc.), miscellaneous tree food crops, non-food treecrops, tree nuts, tropical and subtropical trees and fruit, vine crops,pasture grasses, forage legumes, and rangeland, grass seed or sodproduction, pastures, cotton, corn, soybeans, rice, wheat,greenhouse/shadehouse grown plants, ornamental, plant nurseries,Christmas trees, golf courses and turf, forestry, tobacco, orchids,flowers and roses, foliage crops, algae such as green algae, bryophytes(mosses, liverworts, hornworts), etc. Note that “foliage crops” refersto the types of plants (ferns, etc.) that are typically used in home orcommercial settings for decorative purposes; this alone constitutes avery large commercial industry.

“Plant part” as used herein refers to seeds, roots, leaves, shoots,fruits (e.g., apples, pineapples, citrus fruit, etc.), vegetables,tubers, flowers (e.g., cut flowers such as roses, as well as thereproductive parts of plants), petals, stem, trunk, etc., harvested orcollected from a plant as described herein. The plant part of a vascularplant may be a non-vascular part, such as a seed or meristem (growingtip of a shoot).

“Applying” as described herein can be carried out directly or indirectlyby any suitable technique, including topically applying to the plant orplant part, applying to the media in which the plant or plant part isgrown, stored, displayed or maintained (e.g., adding to water in whichthe stems of cut flowers are placed), etc. Note that the plant may begrown in any suitable media, including but not limited to soil, pottingsoil, soilless media such as sand and hydroponic media (including,solution culture, medium culture, and deep water culture), etc.

“Agricultural composition” as described herein may be in any suitableform, including but not limited to: wettable powders, dry flowables,soluble powders, water dispersibles, liquids, dusts, emulsifiableconcentrates, flowables, fumigants, water dispersible granules, liquidconcentrates, granules, water soluble packages, wettable powders inwater soluble films, emulsions, etc.

“Triazole” refers to the commonly known structures:

“Imidazole” refers to the commonly known structure:

“H” refers to a hydrogen atom. “C” refers to a carbon atom. “N” refersto a nitrogen atom. “O” refers to an oxygen atom. “Halo” refers to F,Cl, Br or I. The term “hydroxy,” as used herein, refers to an —OHmoiety. “Br” refers to a bromine atom. “Cl” refers to a chlorine atom.“I” refers to an iodine atom. “F” refers to a fluorine atom.

An “acyl group” is intended to mean a group —C(O)—R, where R is asuitable substituent (for example, an acetyl group, a propionyl group, abutyroyl group, a benzoyl group, or an alkylbenzoyl group).

“Alkyl,” as used herein, refers to a straight or branched chainhydrocarbon containing from 1 or 2 to 10 or 20 or more carbon atoms(e.g., C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15,etc.). Representative examples of alkyl include, but are not limited to,methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl,tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl,2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl,n-decyl, and the like. In some embodiments, alkyl groups as describedherein are optionally substituted (e.g., from 1 to 3 or 4 times) withindependently selected H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

As generally understood by those of ordinary skill in the art,“saturation” refers to the state in which all available valence bonds ofan atom (e.g., carbon) are attached to other atoms. Similarly,“unsaturation” refers to the state in which not all the availablevalence bonds are attached to other atoms; in such compounds the extrabonds usually take the form of double or triple bonds (usually withcarbon). For example, a carbon chain is “saturated” when there are nodouble or triple bonds present along the chain or directly connected tothe chain (e.g., a carbonyl), and is “unsaturated” when at least onedouble or triple bond is present along the chain or directly connectedto the chain (e.g., a carbonyl). Further, the presence or absence of asubstituent depending upon chain saturation will be understood by thoseof ordinary skill in the art to depend upon the valence requirement ofthe atom or atoms to which the substituent binds (e.g., carbon).

The term “optionally substituted” indicates that the specified group iseither unsubstituted, or substituted by one or more suitablesubstituents. A “substituent” is an atom or atoms substituted in placeof a hydrogen atom on the parent chain or cycle of an organic molecule,for example, H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide.

“Alkenyl,” as used herein, refers to a straight or branched chainhydrocarbon containing from 1 or 2 to 10 or 20 or more carbons, andcontaining at least one carbon-carbon double bond, formed structurally,for example, by the replacement of two hydrogens. Representativeexamples of “alkenyl” include, but are not limited to, ethenyl,2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl,2-heptenyl, 2-methyl-1-heptenyl, 3-decenyl and the like. In someembodiments, alkenyl groups as described herein are optionallysubstituted (e.g., from 1 to 3 or 4 times) with independently selectedH, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide.

“Alkynyl,” as used herein, refers to a straight or branched chainhydrocarbon group containing from 1 or 2 to 10 or 20 or more carbonatoms, and containing at least one carbon-carbon triple bond.Representative examples of alkynyl include, but are not limited, toacetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl, 1-butynyl andthe like. In some embodiments, alkynyl groups as described herein areoptionally substituted (e.g., from 1 to 3 or 4 times) with independentlyselected H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide.

The term “cycloalkyl,” as used herein, refers to a saturated cyclichydrocarbon group containing from 3 to 8 carbons or more. Representativeexamples of cycloalkyl include, cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, cycloalkylgroups as described herein are optionally substituted (e.g., from 1 to 3or 4 times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

“Heterocyclo,” as used herein, refers to a monocyclic or a bicyclic ringsystem. Monocyclic heterocycle ring systems are exemplified by any 5 or6 member ring containing 1, 2, 3, or 4 heteroatoms independentlyselected from the group consisting, of: O, N, and S. The 5 member ringhas from 0 to 2 double bonds, and the 6 member ring has from 0-3 doublebonds. Representative examples of monocyclic ring systems include, butare not limited to, azetidine, azepine, aziridine, diazepine,1,3-dioxolane, dioxane, dithiane, furan, imidazole, imidazoline,imidazolidine, isothiazole, isothiazoline, isothiazolidine, isoxazole,isoxazoline, isoxazolidine, morpholine, oxadiazole, oxadiazoline,oxadiazolidine, oxazole, oxazoline, oxazolidine, piperazine, piperidine,pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridine,pyrimidine, pyridazine, pyrrole, pyrroline, pyrrolidine,tetrahydrofuran, tetrahydrothiophene, tetrazine, tetrazole, thiadiazole,thiadiazoline, thiadiazolidine, thiazole, thiazoline, thiazolidine,thiophene, thiomorpholine, thiomorpholine sulfone, sulfoxide, thiopyran,triazine, triazole, trithiane, and the like. Bicyclic ring systems areexemplified by any of the above monocyclic ring systems fused to an arylgroup as defined herein, a cycloalkyl group as defined herein, oranother monocyclic ring system as defined herein. Representativeexamples of bicyclic ring systems include but are not limited to, forexample, benzimidazole, benzothiazole, benzothiadiazole, benzothiophene,benzoxadiazole, benzoxazole, benzofuran, benzopyran, benzothiopyran,benzodioxine, 1,3-benzodioxole, cinnoline, indazole, indole, indoline,indolizine, naphthyridine, isobenzofuran, isobenzothiophene, isoindole,isoindoline, isoquinoline, phthalazine, pyranopyridine, quinoline,quinolizine, quinoxaline, quinazoline, tetrahydroisoquinoline,tetrahydroquinoline, thiopyranopyridine, and the like. In someembodiments, heterocyclo groups as described herein are optionallysubstituted (e.g., from 1 to 3 or 4 times) with independently selectedH. halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide.

“Aryl” as used herein refers to a fused ring system having one or morearomatic rings. Representative examples of aryl include, azulenyl,indanyl, indenyl, naphthyl, phenyl, tetrahydronaphthyl, and the like.The aryl groups of this invention can be substituted with 1, 2, 3, 4, or5 substituents independently selected from alkenyl, alkenyloxy, alkoxy,alkoxyalkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy,alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, aryl, aryloxy, azido,arylalkoxy, arylalkyl, aryloxy, carboxy, cyano, formyl, halogen,haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, mercapto, nitro, sulfamyl,sulfo, sulfonate. —NR′R″ (wherein, R′ and R″ are independently selectedfrom hydrogen, alkyl, alkylcarbonyl, aryl, arylalkyl and formyl), and—C(O)NR′R″ (wherein R′ and R″ are independently selected from hydrogen,alkyl, alkylcarbonyl, aryl, arylalkyl, and formyl). In some embodiments,aryl groups as described herein are optionally substituted (e.g., from 1to 3 or 4 times) with independently selected H, halo, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide.

“Heteroaryl” means a cyclic, aromatic hydrocarbon in which one or morecarbon atoms have been replaced with heteroatoms. If the heteroarylgroup contains more than one heteroatom, the heteroatoms may be the sameor different. Examples of heteroaryl groups include pyridyl,pyrimidinyl, imidazolyl, thienyl, furyl, pyrazinyl, pyrrolyl, pyranyl,isobenzofuranyl, chromenyl, xanthenyl, indolyl, isoindolyl, indolizinyl,triazolyl, pyridazinyl, indazolyl, purinyl, quinolizinyl, isoquinolyl,quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, isothiazolyl, andbenzo[b]thienyl. Preferred heteroaryl groups are five and six memberedrings and contain from one to three heteroatoms independently selectedfrom the group consisting of: O, N, and S. The heteroaryl group,including each heteroatom, can be unsubstituted or substituted with from1 to 4 suitable substituents, as chemically feasible. For example, theheteroatom S may be substituted with one or two oxo groups, which may beshown as ═O. In some embodiments, heteroaryl groups as described hereinare optionally substituted (e.g., from 1 to 3 or 4 times) withindependently selected H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

“Alkoxy,” as used herein, refers to an alkyl group, as defined herein,appended to the parent molecular moiety through an oxy group, as definedherein. Representative examples of alkoxy include, but are not limitedto, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy,hexyloxy and the like. In some embodiments, alkoxy groups as describedherein are optionally substituted (e.g., from 1 to 3 or 4 times) withindependently selected H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

An “amine” or “amino” is intended to mean the group —NH,. “Optionallysubstituted” amines refers to —NH₂ groups wherein none, one or two ofthe hydrogens is replaced by a suitable substituent as described herein,such as alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl,heteroaryl, alkoxy, carbonyl, carboxy, etc. In some embodiments, one ortwo of the hydrogens are optionally substituted with independentlyselected, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide. Disubstituted amines may have substituents thatare bridging, i.e., form a heterocyclic ring structure that includes theamine nitrogen.

An “amide” as used herein refers to an organic functional group having acarbonyl group (C═O) linked to a nitrogen atom (N), or a compound thatcontains this group, generally depicted as:

wherein, R and R′ can independently be any covalently-linked atom oratoms, for example, H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

A “thiol” or “mercapto” refers to an —SH group or to its tautomer ═S.

A “sulfone” as used herein refers to a sulfonyl functional group,generally depicted as:

wherein, R can be any covalently-linked atom or atoms, for example, H,halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide.

A “sulfoxide” as used herein refers to a sulfinyl functional group,generally depicted as:

wherein, R can be any covalently-linked atom or atoms, for example, H.halohydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide.

The term “oxo,” as used herein, refers to a ═O moiety. The term “oxy,”as used herein, refers to a —O— moiety.

“Nitro” refers to the organic compound functional group —NO₂.

“Carbonyl” is a functional group having a carbon atom double-bonded toan oxygen atom (—C═O). “Carboxy” as used herein refers to a —COONfunctional group, also written as —(C═O)—OH.

“Amino acid sidechain” as used herein refers to any of the 20 commonlyknown groups associated with naturally-occurring amino acids, or anynatural or synthetic homologue thereof. An “amino acid” includes thesidechain group and the amino group, alpha-carbon atom, and carboxygroups, as commonly described in the art. Examples of amino acidsinclude glycine, and glycine that is substituted with a suitablesubstituent as described herein, such as alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, carbonyl, carboxy,etc., or an agriculturally acceptable salt thereof. For example,“Histidine” is one of the 20 most commonly known amino acids foundnaturally in proteins. It contains an imidazole side chain substituent.Other examples of naturally-occurring amino acids include lysine,arginine, aspartic acid, glutamic acid, asparagine, glutamine, serine,threonine, tyrosine, alanine, valine, leucine, isoleucine,phenylalanine, methionine, cryptophan, and cysteine. Also included inthe definitions of “amino acid sidechain” and “amino acid” is proline,which is commonly included in the definition of an amino acid, but istechnically an imino acid. As used in this application, both thenaturally-occurring L-, and the non-natural D-amino acid enantiomers areincluded. The single letter code for amino acids is A (Ala), C (Cys), D(Asp), E (Glu), F (Phe), G (Gly), H (His), I (Ile), K (Lys), L (Leu), M(Met), N (Asn), P (Pro), Q (Gln), R (Arg), S (Ser), T (Thr), V (Val), W(Trp), and Y (Tyr). A “peptide” is a linear chain of amino acidscovalently linked together, typically through an amide linkage, andcontains from 1 or 2 to 10 or 20 or more amino acids, and is alsooptionally substituted and/or branched.

“Agriculturally acceptable salt” is intended to mean a salt that retainsthe biological effectiveness of the free acids and bases of a specifiedcompound and that is not biologically or otherwise undesirable. Examplesof agriculturally acceptable salts include sulfates, pyrosulfates,bisulfates, sulfites, bisulfates, phosphates, monohydrogenphosphates,dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides,bromides, iodides, acetates, propionates, decanoates, caprylates,acrylates, formates, isobutyrates, caproates, heptanoates, propiolates,oxalates, malonates, succinates, suberates, sebacates, fumarates,maleates, butyne-1,4-dioates, hexyne-1,6-dioates, benzoates,chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates,methoxybenzoates, phthalates, sulfonates, xylenesulfonates,phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates,γ-hydroxybutyrates, glycollates, tartrates, methane-sulfonates,propanesulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates,and mandelates.

The term “optionally substituted” indicates that the specified group iseither unsubstituted, or substituted by one or more suitablesubstituents. A “substituent” is an atom or atoms substituted in placeof a hydrogen atom on the parent chain or cycle of an organic molecule.

B. Active Compounds.

Active compounds are provided below. In some of the embodiments providedin the present invention, active compounds are derivatives of triazole.In some embodiments, active compounds include imidazole-triazoleconjugates. In some embodiments, active compounds include2-aminoimidazole-triazole conjugates (“2-AIT”). Active compounds asdescribed herein can be prepared as detailed below or in accordance withknown procedures or variations thereof that will be apparent to thoseskilled in the art.

As will be appreciated by those of skill in the art, the activecompounds of the various formulas disclosed herein may contain chiralcenters, e.g. asymmetric carbon atoms. Thus, the present invention isconcerned with the synthesis of both: (i) racemic mixtures of the activecompounds, and (ii) enantiomeric forms of the active compounds. Theresolution of racemates into enantiomeric forms can be done inaccordance with known procedures in the art. For example, the racematemay be converted with an optically active reagent into a diastereomericpair, and the diastereomeric pair subsequently separated into theenantiomeric forms.

Geometric isomers of double bonds and the like may also be present inthe compounds disclosed herein, and all such stable isomers are includedwithin the present invention unless otherwise specified. Also includedin active compounds of the invention are tautomers (e.g., tautomers oftriazole and/or imidazole) and rotarners.

All chains defined by the formulas herein which include three or morecarbons may be saturated or unsaturated unless otherwise indicated.

Carbons or other atoms along a chain identified by the Formulas hereinmay be identified by number, and when identified by number shall benumbered from left to right. For example:

To illustrate where there are two or more discrete chains, for Formula(II)(i)(a) described below, wherein R², R³, R⁴, R⁵, R⁷ and R⁸═H. andR⁶=phenyl:

the exemplary structure below shows n=5, saturated, one of either R^(x)or R^(y)=methyl at C4; m=3, unsaturated, R^(u)=methyl at C2 (R^(v) isabsent at C2); and R^(x), R^(y), R^(u) and R^(v)═H at all otheroccurrences:

Active compounds for carrying out the present invention includecompounds of Formula

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x) and R^(y) is present or absent (depending uponchain saturation), and is independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide; and

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

As will be appreciated by those of skill in the art, a given substituent(R¹-R⁸) may be present or absent depending upon the valence requirementof the atom or atoms to which the substituent binds (e.g., carbon versusnitrogen).

In some embodiments of Formula (I), R¹ is a substituted amino, A, B, F,G and H are each N, and D and E are each carbon, generally depicted byFormulas (I)(a)(1)-(I)(b)(1):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁶ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide; and

each occurrence of R^(x) and R^(y) is present or absent (depending uponchain saturation), and is independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide; and

n=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide; and

each occurrence of R^(x) and R^(y) is present or absent (depending uponchain saturation), and is independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide; and

n=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (I), R¹ is a substituted amino, A, B, F,G and D are each N, and D and E are each carbon, generally depicted byFormula (I)(b)(2):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x) and R^(y) is present or absent (depending uponchain saturation), and is independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide; and

n=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

Active compounds further include compounds of Formula (I)(i):

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently selected fromthe group consisting. of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

As will be appreciated by those of skill in the art, a given substituent(R¹-R⁸) may be present or absent depending upon the valence requirementof the atom or atoms to which the substituent binds (e.g., carbon versusnitrogen).

In some embodiments of Formula (I)(i), R¹ is a substituted amino; R²,R³, R⁴, R⁵, R⁷ and R⁸═H; A, B, F, G and H are each N, and D and E areeach carbon, generally depicted by Formula (I)(i)(a):

wherein:

R⁶ is selected from the group consisting of: H, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy,amino acid sidechain, amino acid and peptide; and

n=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidedchain, amino acid and peptide.

Active compounds for carrying out the present invention includecompounds of Formula (II):

wherein:

R¹, R², R³, R⁴, R³, R⁶, R⁷ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u) and R^(v) is present or absent(depending upon chain saturation), and is independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20; and

m=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

As will be appreciated by those of skill in the art, a given substituent(R¹-R⁸) may be present or absent depending upon the valence requirementof the atom or atoms to which the substituent binds (e.g., carbon versusnitrogen).

In some embodiments of Formula (II), R¹ is a substituted amino, A, B, F,G and H are each N, and D and E are each carbon, generally depicted byFormula (II)(a):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁶ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u) and R^(v) is present or absent(depending upon chain saturation), and is independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

n=0 to 20; and

m=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (II)(a), R^(1a), R^(1b), R², R³ and R⁵are each H and R⁶ is phenyl, examples of which include, but are notlimited to, the following exemplary Formulas. Each occurrence of R^(x),R^(y), R^(u) and R^(v) present is H unless otherwise indicated.

Formulas (II)(a)(1)(A)-(II)(a)(1)(D), wherein n=1:

M=1: m=2:

m=3: m=3, R^(u)=methyl at C2

Formulas (II)(a)(2)(A)-(II)(a)(2)(D), wherein n=2:

m=1: m=2:

m=3: m=3, R^(u)=methyl at C2:

Formulas (II)(a)(3)(A-(II)(a)(3)(D), wherein n=3:

m=1: m=2:

m=3: m=3, R^(u)=methyl at C2:

Formula (II)(a)(4)(D), wherein n=4; m=3, R^(u)=methyl at C2:

Formula (II)(a)(5)(D), wherein n=5; m=3, R^(u)=methyl at C2:

Formula (II)(a)(6)(D), wherein n=6; m=3, R^(u)=methyl at C2:

Active compounds further include compounds of Formula (II)(i):

wherein:

R¹ and R⁶ are each independently selected from the group consisting of:H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon;

n=0 to 20, saturated or unsaturated; and

m=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (II)(i), R¹ is a substituted amino, A, B,F, G and H are each N, and D and E are each carbon, generally depictedby Formula (II)(i)(a):

wherein:

R^(1a), R^(1b) and R⁶ are each independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, sulfone, sulfoxide,oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

n=0 to 20, saturated or unsaturated; and

m=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (II)(i)(a), R^(1a) and R^(1b) are each H,and R⁶ is heteroaryl, examples of which include, but are not limited to,the following, exemplary Formulas:

Formulas (II)(i)(a)(1)(E)-(II)(i)(a)(1)(L), wherein n=1:

m=1; R⁴ is thiophenyl: m=2; R⁴ is thiophenyl:

m=1; R⁴ is furyl:

m=1; R⁴ is indolyl: m=2; R⁴ is indolyl:

m=1; R⁴ is benzimidazolyl:

Further embodiments include Formulas (II)(i)(a)(2)(E)-(II)(i)(a)(2)(L),wherein n=2; Formulas (II)(i)(a)(3)(E)-(II)(i)(a)(3)(L), wherein n=3;Formulas (II)(i)(a)(4)(E)-(II)(i)(a)(4)(L), wherein n=4; Formulas(II)(i)(a)(5)(E)-(II)(i)(a)(5)(L), wherein n=5; Formulas(II)(i)(a)(6)(E)-(II)(i)(a)(6)(L), wherein n=6; and so on.

These formulas may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

Also provided are compounds of Formula (III):

wherein:

R⁵, R⁶, R⁷, R⁸ and R⁹ are each independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone,sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain,amino acid and peptide; and

A, B, D, E and F are each independently selected from carbon, N, S andO, wherein at least one of A, B, D, E and F is carbon;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

As will be appreciated by those of skill in the art, a given substituent(R⁵-R⁹) may be present or absent depending upon the valence requirementof the atom or atoms to which the substituent binds (e.g., carbon versusnitrogen).

In some embodiments of Formula (III), B, D and E are each N, and A and Fare each carbon, generally depicted as Formula (III)(a):

wherein:

R⁵, R⁶ and R⁹ are each independently selected from the group consistingof: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (III), A, D and E are each N, and B and Fare each carbon, generally depicted as Formula (III)(b):

wherein:

R⁵, R⁶ and R⁹ are each independently selected from the group consistingof: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide; and

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (III)(b), R6 and R9 are each H, generallydepicted by Formula (III)(b)(i):

wherein:

R³ is selected from the group consisting, of: H, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide; and

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (III)(b), R³ and R⁶ are each H, generallydepicted by Formula (III)(b)(ii):

wherein:

R⁹ is selected from the group consisting of: H, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide; and

or an agriculturally acceptable salt thereof

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

Also provided are compounds of Formula (IV):

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R^(s) are each independently selectedfrom the group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(w) ispresent or absent (depending upon chain saturation), and isindependently selected from the group consisting of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20;

m=0 to 20; and

p=0 to 20

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (IV), R¹ is a substituted amino, A, B, F,G and H are each N, and D and E are each carbon, generally depicted byFormula (IV)(a):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁶ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(w) ispresent or absent (depending upon chain saturation), and isindependently selected from the group consisting, of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

n=0 to 20;

m=0 to 20; and

p=0 to 20

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments, R⁶ is a group:

wherein:

X, Y and Z are each independently selected from the group consisting of:H, methyl, Br and Cl.

In some embodiments, R⁶ is a group:

wherein:

R²⁰, R²¹, R²², R²³ and R²⁴ are each independently selected from thegroup consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

Further provided are compounds of Formula (IV)(i):

wherein:

R¹ and R⁶ are each independently selected from the group consisting of:H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (IV)(i), R¹ is a substituted amino, A, B,F, G and H are each N, and D and E are each carbon, generally depictedby Formula (IV)(i)(a):

herein:

R^(1a), R^(1b) and R⁶ are each independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, sulfone, sulfoxide,oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (IV)(i)(a), R^(1a), R^(1b) and R⁶ areeach H. In some embodiments of Formula (IV)(i)(a), R^(1a) and R^(1b) areeach H, and R⁶ is aryl or heteroaryl.

Also provided are compounds of Formula (V):

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(w) ispresent or absent (depending upon chain saturation), and isindependently selected from the group consisting of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20;

m=0 to 20; and

p=0 to 20

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (V), R¹ is a substituted amino. A, B, F,G and H are each N, and D and E are each carbon, generally depicted byFormula (V)(a):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁶ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(w) ispresent or absent (depending upon chain saturation), and isindependently selected from the cuoup consisting of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

n=0 to 20;

m=0 to 20; and

p=0 to 20

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

Further provided are compounds of Formula (V)(i):

wherein:

R¹ and R⁶ are each independently selected from the group consisting of:H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (V)(i), R¹ is a substituted amino, A, B,F, G and H are each N, and D and E are each carbon, generally depictedby Formula (V)(i)(a):

wherein:

R^(1a), R^(1b) and R⁶ are each independently selected from the groupconsisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, sulfone, sulfoxide,oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (V)(i)(a), R^(1a), R^(1b) and R⁶ are eachH, alkyl, cycloalkyl or heterocyclo. In some embodiments of Formula(V)(i)(a), R^(1a) and R^(1b) are each H, and R⁶ is aryl.

Also provided are compounds of Formula (VI):

wherein:

R¹, R², R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are each independently selected fromthe group consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(v) ispresent or absent (depending, upon chain saturation), and isindependently selected from the group consisting of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

A, B, D, E, F, U and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon; and

n=0 to 20;

m=0 to 20; and

p=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (VI), R¹ is a substituted amino, A, B, F,G and H are each N, and D and E are each carbon, generally depicted byFormula (VI)(a):

wherein:

R^(1a), R^(1b), R², R³, R⁵ and R⁶ are each independently selected fromthe group consisting of H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide;

each occurrence of R^(x), R^(y), R^(u), R^(v), R^(z) and R^(w) ispresent or absent (depending upon chain saturation), and isindependently selected from the group consisting of: H, hydroxy, acyl,alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl,alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro,carbonyl, carboxy, amino acid sidechain, amino acid and peptide;

n=0 to 20;

m=0 to 20; and

p=0 to 20;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

Further provided are compounds of Formula (VI)(i):

wherein:

R¹ and R⁶ are each independently selected from the group consisting of:H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

A, B, D, E, F, G and H are each independently selected from carbon, N, Sand O, wherein at least one of D, E, F, G and H is carbon;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted (e.g., from 1 to 3 or 4times) with independently selected H, halo, hydroxy, acyl, alkyl,alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy,amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl,carboxy, amino acid sidechain, amino acid and peptide.

In some embodiments of Formula (VI)(i), R¹ is a substituted amino, A, B,F, G and H are each N, and D and E are each carbon, generally depictedby Formula (VI)(i)(a):

wherein:

R^(1a), R^(1b) and R⁶ are each independently selected from the groupconsisting, of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl,heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, sulfone, sulfoxide,oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide;

n=0 to 20, saturated or unsaturated;

m=0 to 20, saturated or unsaturated; and

p=0 to 20, saturated or unsaturated;

or an agriculturally acceptable salt thereof.

This formula may be optionally substituted from 1 to 3 or 4 times) withindependently selected H, halo, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide.

In some embodiments of Formula (VI)(i)(a), R^(1a) and R^(1b) are each H,and R⁶ is aryl or heteroaryl.

C. Microbicides and Plant Defense Activators.

In some embodiments, an active compound described herein is applied incombination with a microbicide. “Microbicide” as used herein refers to asubstance with the ability to kill or to inhibit the growth ofmicroorganisms (e.g., bacteria, fungal cells, protozoa, etc.), whichmicrobicide is not an active compound in the group herein disclosed oftriazole derivatives. Common microbicides used for microbial control inplants include copper compounds. Examples of copper compounds include,but are not limited to, Bordeaux mixture, copper hydroxide, copperoxychloride, copper sulfate, cuprous oxide, mancopper or oxine-copper.However, microorganisms (e.g., bacteria such as Xanthomonas andPseudomonas) may become resistant to treatment with copper.

In some embodiments, resistant microorganisms (e.g., copper-resistantbacteria) are rendered more susceptible to a microbicides and/or theeffectiveness of treatment with a microbicides is enhanced uponapplication in combination with an active compound described herein(e.g., fruit or vegetable yield is increased as compared to diseasedplant producing the fruit or vegetable that is untreated or treated onlywith the microbicide).

Other microbicides include, but are not limited to, azoles such asazaconazole, bitertanol, propiconazole, difenoconazole, diniconazole,cyproconazole, epoxiconazole, fluquinconazole, flusilazole, flutriafol,hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole,tetraconazole, fenbuconazole, metconazole, myclobutanil, perfurazoate,penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon,triadimenol, triflumizole or triticonazole; pyrimidinyl carbinoles suchas ancymidol, fenarimol or nuarimol; 2-amino-pyrimidine such asbupirimate, dimethirimol or ethirimol; morpholines such as dodemorph,fenpropidin, fenpropimorph, spiroxamin or tridemorph; anilinopyrimidinessuch as cyprodinil, pyrimethanil or mepanipyrim; pyrroles such asfenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl,metalaxyl, R-metalaxyl, ofurace or oxadixyl; benzimidazoles such asbenomyl, carbendazim, debacarb, fuberidazole or thiabendazole;dicarboximides such as chlozolinate, dichlozoline, iprodine,myclozoline, procymidone or vinclozolin; carboxamides such as carboxin,fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidinessuch as guazatine, dodine or iminoctadine; strobilurines such asazoxystrobin, kresoxim-methyl, metominostrobin, SSF-129, methyl2[(2-trifluoromethyl)-pyrid-6-yloxymethyl]-3-methoxy-acrylate or2-[{α[{α-methyl-3-trifluoromethyl-benzyl)imino]-oxy□-o-tolyl]--glyoxylic acid-methylester-O-methyloxime (trifloxystrobin);dithiocarbamates such as ferbam, mancozeb, maneb, metiram, propineb,thiram, zineb or ziram; N-halomethylthio-dicarboximides such ascaptafol, captan, dichlofluanid, fluoromide, folpet or tolyfluanid;nitrophenol derivatives such as dinocap or nitrothal-isopropyl; organophosphorous derivatives such as edifenphos, iprobenphos, isoprothiolane,phosdiphen, pyrazophos or toclofos-methyl; and other compounds ofdiverse structures such as acibenzolar-S-methyl, hatpin, anilazine,blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil,dichione, diclomezine, dicloran, diethofencarb, dimethomorph, dithianon,etridiazole, famoxadone, fenamidone, fentin, ferimzone, fluazinam,flusulfamide, fenhexamid, fosetyl-aluminium, hymexazol, kasugamycin,methasulfocarb, pencycuron, phthalide, polyoxins, probenazole,propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide,tricyclazole, triforine, validamycin,(S)-5-methyl-2-methylthio-5-phenyl-3-phenylamino-3,5-di-hydroimidazol-4-o-ne(RPA 407213),3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281), N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON 65500),4-chloro-4-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfon-amide(IKF-916),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)-propionamide (AC382042) or iprovalicarb (SZX 722).

An “antibiotic” as used herein is a type of “microbicide.” Commonantibiotics include aminoglycosides, carbacephems (e.g., loracarbef),carbapenems, cephalosporins, glycopeptides (e.g., teicoplanin andvancomycin), macrolides, monobactams (e.g., aztreonam) penicillins,polypeptides (e.g., bacitracin, colistin, polymyxin B), quinolones,sulfonamides, tetracyclines, etc. Antibiotics treat infections by eitherkilling, or preventing the growth of microorganisms. Many act to inhibitcell wall synthesis or other vital protein synthesis of themicroorganisms.

Aminoglycosides are commonly used to treat infections caused byGram-negative bacteria. Examples of aminoglycosides include, but are notlimited to amikacin, gentamicin, kanamycin, neomycin, netilmicin,streptomycin, tobramycin, and paromomycin.

Carbapenems are broad-spectrum antibiotics, and include, but are notlimited to, ertapenem, doripenem, imipenem/cilstatin, and meropenem.

Cephalosporins include, but are not limited to, cefadroxil, cefazolin,cefalotin (cefalothin), cefalexin, cefaclor, cefamandole, cefoxitin,cefprozil, loracarbef, cefuroxime, cefixime, cefdinir, cefditoren,cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten,ceftizoxime, ceftriaxone, cefepime, cefpirome, and ceftobiprole.

Macrolides include, but are not limited to, azithromycin,clarithromycin, dirithromycin, erythromycin, roxithromycin,troleandomycin, telithromycin and spectinomycin.

Penicillins include, but are not limited to, amoxicillin, ampicillin,azlocillin, bacampicillin, carbenicillin, cloxacillin, dicloxacillin,flucloxacillin, mezlocillin, meticillin, nafcillin, oxacillin,penicillin, piperacillin and ticarcillin.

Quinolones include, but are not limited to, ciprofloxacin, enoxacin,gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin,norfloxacin, ofloxacin and trovafloxacin.

Sulfonamides include, but are not limited to, mafenide, prontosil,sulfacetamide, sulfamethizole, sulfanilamide, sulfasalazine,sulfisoxazole, trimethoprim, and co-trimoxazole(trimethoprim-sulfamethoxazole).

Tetracyclines include, but are not limited to, demeclocycline,doxycycline, minocycline, oxytetracycline and tetracycline.

Other antibiotics include arsphenamine, chloramphenicol, clindamycin,lincomycin, ethambutol, fosfomycin, fusidic acid, furazolidone,isoniazid, linezolid, metronidazole, mupirocin, nitrofurantoin,platensimycin, pyrazinamide, quinupristin/dalfopristin, rifampin(rifampicin), tinidazole, etc.

Other microbicides that may be used in combination with the activecompounds of the present invention include bacteriophages (bacterialviruses) such as Bacillus. Examples of bacteriophage microbicidesinclude, but are not limited to, AgriPhage™ (OmniLytics, Inc., Salt LakeCity, Utah) and Serenade® (AgraQuest, Davis, Calif.). See, e.g., U.S.Pat. Nos. 5,919,447 and 6,077,506 to Marrone et al.; U.S. Pat. No.6,103,228 to Heins et al.; and U.S. Patent Application Publication20080152684.

In some embodiments, an active compound described herein is applied incombination with a plant defense activator. A “plant defense activator”as used herein is a compound that improves disease resistance byactivatinv, a plant's natural defense mechanisms, e.g., induces theplant to produce disease-fighting compounds. Examples of plant defenseactivators include, but are not limited to, prohexadione-calcium(Apogee), Cropset (plant booster element complex), probenazole,potassium phosphate (e.g., ProPhyt®, Helena Chemical Company), hatpinprotein (e.g., Messenger®, Eden Biosciences Ltd, Bothell, Wash.),acibenzolar or acibenzolar-S-methyl (e.g., Actigard™, Syngenta CropProduction, Inc, Greensboro, N.C.), streptomycin sulfate, reynoutriasachalinensis extract (reysa), etc.

D. Agrochemical Compositions.

Active compounds of the present invention can be used to prepareagrochemical compositions in like manner as other antimicrobialcompounds. See, e.g., U.S. Pat. Application 2006/0094739; see also U.S.Pat. Nos. 6,617,330; 6,616,952; 6,569,875; 6,541,500, and 6,506,794.

Active compounds described herein can be used for protecting, plantsagainst diseases that are caused by microorganisms, includingbiofilm-forming microorganisms. The active compounds can be used in theagricultural sector and related fields as active ingredients forcontrolling plant pests. The active compounds can be used to inhibit ordestroy the pests that occur on plants or parts of plants (fruit,blossoms, leaves, stems, tubers, roots) of different crops of usefulplants, optionally while at the same time protecting also those parts ofthe plants that grow later e.g. from phytopathogenic microorganisms.

Active compounds may be used as dressing agents for the treatment ofplant propagation material, in particular of seeds (fruit, tubers,grains) and plant cuttings (e.g. rice), for the protection againstfungal infections as well as against phytopathogenic fungi occurring inthe soil.

The active compounds can be used in the form of compositions and can beapplied to the crop area or plant to be treated, simultaneously or insuccession with further compounds. These further compounds can be e.g.fertilizers or micronutrient donors or other preparations whichinfluence the growth of plants. They can also be selective herbicides aswell as insecticides, fungicides, bactericides, nematicides,molluscicides, plant growth regulators, plant activators or mixtures ofseveral of these preparations, if desired together with furthercarriers, surfactants or application promoting adjuvants customarilyemployed in the art of formulation.

Suitable carriers and adjuvants can be solid or liquid and aresubstances useful in formulation technology, e.g. natural or regeneratedmineral substances, solvents, dispersants, wetting agents, tackifiers,thickeners, binders or fertilizers.

The active compounds are used in unmodified form or, preferably,together with the adjuvants conventionally employed in the art offormulation. To this end they are conveniently formulated in knownmanner to emulsifiable concentrates, coatable pastes, directly sprayableor dilutable solutions, dilute emulsions, wettable powders, solublepowders, dusts, granulates, and also encapsulations e.g. in polymericsubstances. As with the type of the compositions, the methods ofapplication, such as spraying, atomizing, dusting, scattering, coatingor pouring, are chosen in accordance with the intended objectives andthe prevailing circumstances.

The formulation, i.e. the compositions containing the active compoundand, if desired, a solid or liquid adjuvant, are prepared in knownmanner, typically by intimately mixing and/or grinding the compound withextenders, e.g. solvents, solid carriers and, optionally, surface activecompounds (surfactants).

Suitable carriers and adjuvants may be solid or liquid and correspond tothe substances ordinarily employed in formulation technology, such as,e.g. natural or regenerated mineral substances, solvents, dispersants,wetting agents, tackifiers, thickeners, binding agents or fertilizers.Such carriers are for example described in WO 97/33890.

Further surfactants customarily employed in the art of formulation areknown to the expert or can be found in the relevant literature.

The agrochemical formulations will usually contain from 0.1 to 99% byweight, preferably from 0.1 to 95% by weight, of a compound describedherein, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of asolid or liquid adjuvant, and from 0 to 25% by weight, preferably from0.1 to 25% by weight, of a surfactant.

Whereas it is preferred to formulate commercial products asconcentrates, the end user will normally use dilute formulations.

The compositions may also contain further adjuvants such as stabilizers,antifoams, viscosity regulators, binders or tackifiers as well asfertilizers, micronutrient donors or other formulations for obtainingspecial effects.

E. Methods of Use.

Target crops or plants to be treated with active compounds andcompositions of the invention typically comprise the following speciesof plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum andrelated species); beet (sugar beet and fodder beet); pomes, drupes andsoft fruit (apples, pears, plums, peaches, almonds, cherries,strawberries, raspberries and blackberries); leguminous plants (beans,lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives,sunflowers, coconut, castor oil plants, cocoa beans, groundnuts);cucumber plants (pumpkins, cucumbers, melons); fiber plants (cotton,flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit,mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots,onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamon,camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane,tea, pepper, vines including grape-bearing vines, hops, bananas,pineapple, turf and natural rubber plants, as well as ornamentals(flowers, shrubs, broad-leafed trees and evergreens, such as conifers).This list does not represent any limitation.

1. Bacterial infections. The methods, active compounds and compositionscan be used to treat bacterial infections in a variety of plants, withspecific examples including but not limited to those set forth below.

Citrus. In citrus trees (including orange, lemon, lime, and grapefruit)active compounds and compositions as described herein can be used totreat or control a variety of microbial diseases, including but notlimited to canker (caused by Xanthomonas campestris or Xanthomonasaxonopodis infection), bacterial spot (caused by Xanthomonas campestrispv. Citrumelo infection); Black Pit(fruit) (caused by Pseudomonassyringae infection); Blast (caused by Pseudomonas syringae infection)citrus variegated chlorosis (caused by Xylella fastidiosa infection),and Citrus Huanglongbing (HLB) caused by Candidatus Liberibacterasiaticus.

Pome Fruit. In pome fruits (including apple, pear, quince, Asian pear,and loquat), active compounds and compositions as described herein canbe used to treat or control a variety of microbial infections, includingbut not limited to Fire Blight (caused by Erwinia amylovora infection),Crown Gall (caused by Agrobacterium tumefaciens infection); Blister spot(caused by Pseudomonas syringae infection) and Hairy root (caused byAgrobacterium rhizogenes infection).

Peppers. In pepper plants, active compounds and compositions asdescribed herein can be used to treat or control a variety of microbialinfections, including but not limited to: Bacterial Spot (caused byXanthomonas campestris pv. vesicatoria infection); Bacterial wilt(caused by Ralstonia solanacearune infection), and Syringae seedlingblight and leaf spot (caused by Pseudomonas styingae infection).

Tomatoes. In tomato plants, active compounds and compositions asdescribed herein can be used to treat or control a variety of microbialinfections, including but not limited to: Bacterial canker (caused byClavibacter michiganesis), Bacterial speck (caused by Pseudomonassyringae), Bacterial spot (caused by Xanthomonas campestrisvesicatoria), Bacterial stern rot and fruit rot (caused by Erwiniacarotovora), Bacterial wilt (caused by Ralstonia solanacearum), Pithnecrosis (caused by Pseudomonas corrugate), and Syringae leaf spot(caused by Pseudomonas syringae).

Soybeans. In soybeans, active compounds and compositions as describedherein can be used to treat or control a variety of microbialinfections, including but not limited to: Bacterial blight (caused byPseudomonas amygdale), Bacterial pustules (caused by Xanthomonasaxonopodis pv. Glycines), and Bacterial wilt (caused by Ralstoniasolanacearum or Curtobacterium flaccumfaciens).

Corn, Cotton, Wheat and Rice. In corn, cotton, wheat and rice, activecompounds and compositions as described herein can be used to treat orcontrol a variety of microbial infections, including but not limited to:bacterial blights, leaf spots and leaf streak caused by Xanthomonasspecies; bacterial sheath rot, stripe and spot caused by Pseudomonasspecies; and to bacterial stalk and top rot, wilt, foot rot, pink seedand lint degradation caused by Erwinia species.

Pineapple. In pineapple, active compounds and compositions as describedherein can be used to treat or control a variety of microbialinfections, including but not limited to: Bacterial heart rot and Fruitcollapse (caused by Erwinia chrysanthemi), Bacterial fruitlet brown rot(caused by Erwinia ananas), Marbled fruit and Pink fruit (caused byErwinia herbicola), Soft rot (caused by Erwinia carotovora), and Aceticsouring (caused by Acetic acid bacteria).

The above listing is but a sampling, and active compounds andcompositions as described herein may also be used to treat or controlbacteria (some of which are named above) in a variety of plants. Forexample, the bacteria Xylella fastidiosa infects citrus trees as notedabove (citrus variegated chlorosis), and also infects grapevines(Pierce's disease). Other plant hosts of Xylella fastidiosa include, butare not limited to, ornamentals, oleander (leaf scorch), almond, coffee,maple, mulberry, elm, sycamore, alfalfa, etc. Similarly, Ralstoniasolanacearum infects soybeans (bacterial wilt) as well as banana (Mokodisease), tobacco (Granville wilt), geranium (southern bacterial wilt),potato (brown rot) and a wide variety of other plants, including gingerand mulberry.

2. Fungal infections. In addition to treating or controlling bacterialinfections, active compounds and compositions as described herein can beused to treat or control fungal infections such as rots, leaf molds,blights, wilts, damping-off, spot, root rot, stem rot, mildew, brownspot, gummosis, melanose, post-bloom fruit drop, scab, alternaria,canker, flyspeck, fruit blotch, dieback, downy mildews, ear rots,anthracnose bunts, smut, rust, eyespot and pecky rice. Genera ofplant-pathogenic fungi that can be treated or controlled by the activecompounds, compositions, and methods described herein include but arenot limited to: Pythium spp., Fusarium spp., Rhizoctonia spp.,Cercospora spp., Alternaria spp., Colletotrichum spp., Ustilago spp.,Phoma spp., Gibberella spp. Penicillium spp., Gloinerella spp. Diplodiaspp., Curvularia spp., Sclerospora spp., Peronosclerospora spp.,Cercospora spp., Puccinia spp., Ustilago spp., Aspergillus spp.,Phomopsis spp., Diaporthe spp., Botrytis spp., Verticillium spp.,Phytophthors spp.

Particular fungal infections that can be treated or controlled by themethods, compounds and compositions described herein, in vegetables andgreenhouse crops, include Phytophthora blight (caused by Phytophthoracapsici) and Pythium damping-off (caused by Pythium spp).

Note that Phytophthora also has adverse effects on crops ranging frompineapples to cotton. It can kill woody citrus seedlings and youngcitrus trees (oranges, grapefruits, lemons, limes). In the greenhouse,germinating seed and seedlings are very susceptible to damping-offcaused by Phytophthora, Pythium, Sclerotina and Rhizoctonia species. Thecost to the grower to lose his crop to any of these fungi issubstantial. The loss can happen at transplant time or when the crop isready to be harvested.

The problems of fungi are not restricted to traditional crops but alsoextend to forestry products and have worldwide scope. Phytophthorctcinnamonzi is a soil-borne water mould that leads to a condition inplants called “root rot” or “dieback.” P. cinnamomi causes root rotaffecting woody ornamentals including azalea, dogwood, forsythia, Fraserfir, hemlock, Japanese holly, juniper, rhododendron, white pine, andAmerican chestnut. P. cinnamomi is responsible for the destruction ofthe elegant American chestnut tree. In Australia, P. cinnamomi hasspread through the forests of western Australia, and into coastalforests of Victoria, where entire plant ecosystems are beingobliterated. Given that P. cinnamomi is a soil-borne water mould thatinfects the roots, almost the entire action takes place below ground.This problem highlights the importance of developing new compounds tocounter fungal infections, even those that directly affect only theroots of the plant rather than the more visible effects on fruits orvegetables.

Active compounds of the invention can be applied to plants or plant lociin accordance with known techniques. The compound(s) can be tank mixedwith other agricultural, turf, ornamental nursery, forestry and allother plant-labeled compatible pesticides. The compound(s) can beapplied to seed. The compound(s) can be applied to edible and non-ediblecrops. The compound(s) can be applied to roots and all other parts ofall plants. The compound(s) can be applied in greenhouses. Thecompound(s) can be applied and used in food-processing facilities. Thecompound(s) can be applied to plastic food bags and containers. Thecompound(s) can be applied as a solid, as its free base, or as a salt.The salts can include, but are not limited to, HI, HCl, HBr, H₂SO₄,acetic acid, and trifluoroacetic acid. The compound(s) can applied as asolution from 0.0001% to 99.9%. The compound(s) can be applied as asolid or solution with copper-based cidal compounds. The compound(s) canbe applied with specific additional active agents, including but notlimited to bactericides, fungicides, pesticides, biological insecticidesand microbial insecticides.

Application can be carried out with any suitable equipment or technique,such as: Aerial—Fixed wing. and Helicopter; Ground Broadcast Spray—Boomor boomless system, pull-type sprayer, floaters, pick-up sprayers, spraycoupes, speed sprayers, and other broadcast equipment, water wagons andwater bags; Low pressure boom sprayers, High pressure sprayers; Airblast sprayers; Low volume air sprayers (mist blowers); Ultra-low volumesprayers (ULV); Aerosol Generators (foggers); Dusters; Soil Injector;Hand-Held or High-Volume Spray Equipment—knapsack and backpack sprayers,pump-up pressure sprayers, hand guns, motorized spray equipment;Selective Equipment—Recirculating sprayers, shielded and hoodedsprayers; Controlled droplet applicator (CDA) hand-held or boom-mountedapplicators that produce a spray consisting of a narrow range of dropletsize; Any and all greenhouse sprayers; Micro-sprinkler or dripirrigation systems; Chemigation.

One method of applying an active compound of the invention, or anagrochemical composition which contains at least one of said compounds,is foliar application. The frequency of application and the rate ofapplication will depend on the risk of infestation by the correspondingpathogen. However, the active compounds can also penetrate the plantthrough the roots via the soil (systemic action) by drenching the locusof the plant with a liquid formulation, or by applying the compounds insolid form to the soil, e.g. in granular form (soil application). Incrops of water such as rice, such granulates can be applied to theflooded rice field. The active compounds may also be applied to seeds(coating) by impregnating the seeds or tubers either with a liquidformulation of the fungicide or coating them with a solid formulation.

The term locus as used herein is intended to embrace the fields on whichthe treated crop plants are growing, or where the seeds of cultivatedplants are sown, or the place where the seed will be placed into thesoil. The term seed is intended to embrace plant propagating materialsuch as cuttings, seedlings, seeds, and germinated or soaked seeds.

Advantageous rates of application are normally from 5 g to 2 kg ofactive ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kga.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seeddrenching agent, convenient dosages are from 10 mg to 1 g of activesubstance per kg, of seeds.

F. Combination Treatments.

In some embodiments, methods of enhancing the effects of a microbicide(such as a microbicide comprising copper, e.g., Kocide® 2000 or Kocide®3000 (DuPont™, with active ingredient copper hydroxide) are disclosed,comprising the step of applying an active compound in combination with amicrobicide, the active compound being applied in an amount effective toenhance the effects of the microbicide.

In some embodiments, methods of enhancing the effects of a plant defenseactivator are disclosed, comprising the step of applying an activecompound in combination with a plant defense activator, the activecompound being applied in an amount effective to enhance the effects ofthe plant defense activator.

“Enhancing” the effects of a microbicide by applying an active compoundin combination with the microbicide refers to increasing theeffectiveness of the microbicide, such that the microorganism killingand/or growth inhibition is higher at a certain concentration of themicrobicide applied in combination with the active compound thanwithout. In some embodiments, a bacteria or other microorganism is“sensitized” to the effects of a microbicide, such that the bacteria orother microorganism that was resistant to the microbicide prior toapplying the active compound (e.g., little to none, or less than 20, 10,5 or 1% are killed upon application) is rendered vulnerable to thatmicrobicide upon or after applying the active compound (e.g., greaterthan 20, 30, 40, 50, 60, 70, 80, 90, or 95% or more are killed).

Similarly, “enhancing” the effects of a plant defense activator byapplying an active compound in combination with the plant defenseactivator refers to increasing the effectiveness of the plant defenseactivator, such that the microorganism killing and/or growth inhibitionis higher at a certain concentration of the plant defense activatorapplied in combination with the active compound than without. In someembodiments, a bacteria or other microorganism is “sensitized” to theeffects of a plant defense activator, such that the bacteria or othermicroorganism that was resistant to the effects of the plant defenseactivator prior to applying the active compound (e.g., little to none,or less than 20, 10, 5 or 1% are killed upon application) is renderedvulnerable to the effects of that plant defense activator upon or afterapplying the active compound (e.g., greater than 20, 30, 40, 50, 60, 70,80, 90, or 95% or more are killed).

As used herein, the application of two or more compounds (inclusive ofactive compounds and microbicides) “in combination” means that the twocompounds are applied closely enough in time that the application of orpresence of one alters the biological effects of the other. The twocompounds may be applied simultaneously (concurrently) or sequentially.

Simultaneous application of the compounds may be carried out by mixingthe compounds prior to application, or by applying the compounds at thesame point in time but at different sites of the plant or usingdifferent types of applications, or applied at times sufficiently closethat the results observed are indistinguishable from those achieved whenthe compounds are applied at the same point in time.

Sequential application of the compounds may be carried out by applying,e.g., an active compound at some point in time prior to application of amicrobicide, such that the prior application of active compound enhancesthe effects of the microbicide (e.g., percentage of microorganismskilled and/or slowing the growth of microorganisms). In someembodiments, an active compound is applied at some point in time priorto the initial application of a microbicide. Alternatively, themicrobicide may be applied at some point in time prior to theapplication of an active compound, and optionally, applied again at somepoint in time after the application of an active compound.

EXAMPLES Example 1 Synthesis of 2-aminoimidazole-triazole (2-AIT)Chemical Library

There is a paucity of reactions that have been reported to be compatiblewith 2-aminoimidazoles. To test the applicability of the Cu(I)-catalyzed[3+2] alkyne/azide cycloaddition (Click reaction, see Kolb et al.,Angewandte Chemie-International Edition 2001, 11, 2004-2021; Rodionov etal., Angewandte Chemie-International Edition 2005, 15, 2210-2215), wesynthesized the alkyne derived 2-aminoimidzole 1 and tested its abilityto participate in a Cu(I)-catalyzed [3+2] cycloaddition with benzylazide.

The alkyne derived 2-aminoimidazole (2-AI) was synthesized as outlinedin Scheme 1. Amino acid 2 (Kotha et al., Tetrahedron 2002, 45,9203-9208) was subjected to small scale Akabori reduction (Akabori,Berichte Der Deutschen Chemischen Gesellschaft 1933, 66, 151-158),which, followed by condensation with cyanamide (Xu Yz et al., J Org Chem1997, 3, 456-464) delivered the target alkyne 2-AI 1 in 88% yield. With1 in hand, we explored various conditions to elicit the Cu-catalyzed[3+2] cycloaddition between 1 and benzyl azide (Table 1).

TABLE 1

Scale (mg) Cu(I) Source^(a) Solvent Base Temp Yield 20 CuI THF DIEA RTNR 20 CuI THF DIEA 40° C. NR 20 CuSO₄/NaAsc EtOH/H₂O (1:1) — RT NR 20CuSO₄/NaAsc EtOH/H₂O (1:1) — 40° C. 86% 100  CuSO₄/NaAsc EtOH/H₂O (1:1)— 40° C. Decomp 100  CuSO₄/NaAsc t-BuOH/H₂O/ — RT 93% CH₂Cl₂ (1:1:1)^(a)NaAsc = Sodium Ascorbate

Reactions in THF using, Cu(I) yielded no reaction and only returnedstarting material. We then switched to using CuSO₄ and sodium ascorbatein a 1:1 solvent mixture of H₂O/EtOH. Again, no reaction was noted.However, when the reaction was heated to 40° C. we noted cleanconversion to the desired 2-AIT conjugate 3 in 86% yield. Unfortunately,when the reaction was scaled up, we observed a significant amount ofdecomposition. Room temperature click reactions have been noted when a1:1:1 solvent mixture of H₂O/EtOH/CH₂Cl₂ (Lee et al., TetrahedronLetters 2006, 29, 5105-5109) is employed instead of the 1:1 H₂O/EtOHmixture. When these reaction conditions were tested, we observedconversion to 3 in 93% yield.

With the methodology established to access 2-AIT conjugates, we employedthe synthetic approach outlined in Scheme 1 to synthesize 2-AI alkynes 4and 5 in which we systematically extended the methylene space betweenthe alkyne and the 2-AI. The click reaction was then performed betweeneach of the 2-AI alkynes and 12 azides to yield an initial 2-AIT library(shown below). Each compound was characterized (¹H NMR, ¹³C NMR, HRMS).

In conclusion, we have developed a synthetic approach to access2-aminoimidazole/triazole (2-AIT) conjugates that is underpinned by theCu(I)-catalyzed [3+2] alkyne/azide cycloaddition. Using, this chemistrywe have assembled a focused library of 2-AIT conjugates.

1. Experimental Protocols for 2-AIT Conjugate Synthesis

All reagents used for chemical synthesis were purchased fromcommercially available sources and used without further purification.Chromatography was performed using 60 A mesh standard grade silica gelfrom Sorbtech (Sorbent Technologies, Inc., Atlanta, Ga.). NMR solventswere obtained from Cambridge Isotope Laboratories, Inc. (Andover, Mass.)and used as received. ¹H NMR (300 MHz or 400 MHz) and ¹³C NMR (75 MHz or100 MHz) spectra were recorded at 25° C. on Varian Mercuryspectrometers. Chemical shifts (6) are given in ppm relative totetramethylsilane or the respective NMR solvent; coupling constants (J)are in hertz (Hz). Abbreviations used are s=singlet, bs=broad singlet,d=doublet, dd=doublet of doublets, t=triplet, dt=doublet of triplets,bt=broad triplet, qt=quartet, m=multiplet, bm=broad multiplet andbr=broad. High and low resolution mass spectra were obtained at theNorth Carolina State Mass Spectrometry Laboratory for Biotechnology. FABexperiments were carried out with a JOEL HX110HF mass spectrometer whileESI experiments were carried out on an Agilent LC-TOF massspectrometers.

Chemical Library:

Synthesis:

To a 50 mL round-bottomed flask equipped with a magnetic stirbar wasadded 3-furan methanol (1.00 g, 10.2 mmol) and a solution of diphenylphosphoryl azide (3.37 g, 12.2 mmol) in toluene (30 mL). The stirringsolution is allowed to cool to 0° C. in which 1,8 Diazabycyclo [5.4.0.]undec-7-ene (1.86 g, 12.2 mmol) was added dropwise. The reaction isallowed to slowly warm to ambient temperature for an additional 16 hoursof stirring. After this period, the reaction mixture is washed withwater (2×20 mL) and then with 5% HCl (20 mL). Volatiles are evaporatedunder reduced pressure. The resulting residue is then purified by columnchromatography (1:9 ethyl acetate/hexane) providing 3-azidomethyl furan(1.19 g, 95%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃) δ 7.46 (d,1H), δ 7.44 (s, 1H), δ 6.42 (d, 1H), δ 4.20 (s, 2H). ppm; ¹³C NMR (75MHz, CDCl₃) δ 144.1, 141.1, 110.4, 92.1, 45.8 ppm; LRMS (EI) calcd forC₅H₅N₃O (M+) 123, found 123.

Following the same procedure used to synthesize 3-azidomethyl furan,indole-3-methanol (2.00 g, 13.6 mmol) was converted to 3-azodomethylindole (1.31 g, 56%) as a yellow oil. ¹H NMR (300 MHz, CDCl₃) δ 8.19(bs, 1H), δ 7.71 (d, 1H), δ 7.39 (m, 2H), δ 7.19 (m, 2H), δ 4.54 (s, 2H)ppm; ₁₃C NMR (75 MHz, CDCl₃) δ 130.3, 125.9, 125.3, 122.2, 120.3, 120.3,119.7, 118.7, 111.9 ppm; LRMS (EI) calcd for C₉H₈N₄ (M+) 172, found 172.

Following the same procedure used to synthesize 3-azidomethyl furan,furfuryl alcohol (2.50 g, 25.5 mmol) was converted to 2-azidomethylfuran (2.96 g, 95%) as a colorless oil. ¹H. NMR (300 MHz, CDCl₃) δ 7.43(d, 1H), δ 6.36 (m, 2H), δ 4.29 (s, 2H) ppm; ₁₃C NMR (75 MHz, CDCl₃) δ148.2, 110.7, 109.6, 47.2 ppm; LRMS (EI) calcd for C₅H₅N₃O (M+) 123,found 123.

Following the same procedure used to synthesize 3-azidomethyl furan,thiophene-3-methanol (3.14 g, 27.6 mmol) was converted to 3-azidomethylthiophene (3.72 g, 97%) as a colorless oil. ¹H NMR (300 MHz, CDCl₃) δ7.38 (d, 1H), δ 7.23 (s, 1H), δ 7.10 (d, 1H) δ 4.36 (s, 2H) ppm; ¹³C (75MHz, CDCl₃) δ 136.4, 127.6, 127.1, 124.0 49.9 ppm; LRMS (EI) calcd forC₅H₅N₃S (M+) 139, found 139.

2-chloroethyl-5, 6-dimethyl-1H-benzimidazole was synthesized through thetreatment of 4,5-dimethyl-1,2-phenylenediamine to conditions outlined byHortelano (Raban et al., Org. Chem. 1985, 50 (13), 2205-2210). Theresulting product was transformed to2-azidomethyl-5,6-dimethyl-1H-benzimidazole following conditionsoutlined by Hankovszky resulting in a yellow solid (Hiales et al.,Synthesis 1978, 4, 313-315). H NMR (300 MHz, CDCl₃) δ 7.26 (s, 2H), δ4.72 (s, 2H), δ 2.37 (s, 6H) ppm; ₁₃C NMR (75 MHz, DMSO) δ 153.7, 134.3,130.1, 125.1, 124.6, 117.2, 113.6, 48.0, 20.6, 19.6 ppm; HRMS (FAB)calcd for C₁₀H₁₁N₅ (M+) 201.1014, found 201.1010.

To a 100 mL round-bottomed flask equipped with a magnetic stir was addedtrans-2-methyl-3-phenyl-2-propen-1-ol (2.00 g, 13.5 mmol) and 75 mL ofmethylene chloride. The solution was then cooled to 0° C. whilestirring. Then, triethylamine (2.75 g, 27.0 mmol) is added followed by adropwise addition of methanesulfonyl chloride (2.34 g, 20.4 mmol) and atwo hour stir period. The reaction mixture is washed with water (2×75mL), dried with sodium sulfate and then concentrated de vacuo. The crudemixture is then dissolved in 75 mL of DMF and then stirred via magneticstir bar. To this mixture, sodium azide (1.76 g, 27.0 mmol) is added.The reaction mixture is then heated to 80° C. and allowed to stir fortwo hours. At this time, volatiles are concentrated de vacuo and theresulting residue is purified via column chromatography (1:9 ethylacetate/hexane) providing, (3-Azido-2-methyl propenyl)-benzene (2.08 g,89%) as a colorless oil. ₁H NMR (300 MHz, CDCl₃) δ 7.36-7.25 (m, 5H), δ6.53 (s, 1H), δ 3.87 (s, 2H) ppm; ₁₃C NMR (75 MHz, CDCl₃) δ 129.4,129.2, 128.9, 128.6, 128.4, 127.1, 59.9, 52.0, 22.3, 16.5 ppm; LRMS (EI)calcd for C₁₀H₁₁N₃ (M+) 173, found 173.

Following, the same procedure used to synthesize(3-Azido-2-methyl-propenyl)benzene, thiophene-3-ethanol (2.00 g, 15.5mmol) was converted to 3-azidoethyl-thiophene (2.06 g, 86%) as acolorless oil. ₁H NMR (300 MHz, CDCl₃) δ 7.36 (s, 1H), δ 7.14 (d, 1H), δ7.04 (d, 1H), δ 3.54 (t, 2H), δ 2.98 (t, 2H) ppm; ₁₃C NMR (75 MHz,CDCl₃) δ 138.7, 128.4, 126.3, 122.2, 52.0, 30.1 ppm; LRMS (EI) calcd forC₆H₇N₃S (M+) 153, found 153.

2-Amino-hex-5-ynoic acid methyl ester hydrochloride was synthesizedusing the same methods previously reported for the synthesis of2-Amino-pent-4-ynoic acid methyl ester hydrochloride (Kotha et al.,Tetrahedron 2002, 58, 9203-9208). ₁H NMR (300 MHz, D20) δ 4.16 (t, 1H).δ 3.71 (s, 3H), δ 2.32 (t, 1H), δ 2.29 (m, 2H), δ 2.06 (m, 2H) ppm; ₁₃CNMR (75 MHz, D₂O) δ 170.4, 82.4, 71.4, 53.9, 52.1, 28.7, 14.4 ppm; HRMS(ESI) calcd for C₇H₁₁NO₂ (M+) 142.0859, found 142.862.

2-Amino-hept-6-ynoic acid methyl ester hydrochloride was synthesizedusing the same methods previously reported for the synthesis of2-Amino-pent-4-ynoic acid methyl ester hydrochloride (Kotha et al.,Tetrahedron 2002, 58, 9203-9208). ₁H NMR (300 MHz, DMSO) δ 8.75 (s, 2H),δ 3.99 (m, 1H), δ 3.72 (s, 3H), δ 2.82 (t, 1H), δ 2.17 (m, 2H), δ 1.89(m, 2H), δ 1.51 (m, 2H) ppm; ₁₃C NMR (75 MHz, DMSO) δ 163.7, 83.1, 69.2,60.9, 30.6, 29.5, 23.9, 17.6 ppm; HRMS (ESI) calcd for C₈H₁₃NO₂ (M+)156.1019, found 156.1017.

2-Amino-oct-7-ynoic acid methyl ester hydrochloride was synthesizedusing the same methods previously reported for the synthesis of2-Amino-pent-4-ynoic acid methyl ester hydrochloride (Kotha et al.,Tetrahedron 2002, 58, 9203-9208). ₁H NMR (300 MHz, D₂O) δ 4.16 (t, 1H),δ 3.84 (s, 3H), δ 2.35 (t, 1H), δ 2.24 (m, 2H), δ 1.95 (m, 2H), δ 6 1.52(m, 4H) ppm; ₁₃C NMR (75 MHz, D₂O) δ 170.9, 85.6, 69.6, 53.6, 52.9,29.3, 27.0, 23.4, 17.3 ppm; HRMS (ESI) calcd for C₉H₁₅NO₂ (M+) 170.1176,found 170.1171.

2-Amino-non-8-ynoic acid methyl ester hydrochloride was synthesizedusing the same methods previously reported for the synthesis of2-Amino-pent-4-ynoic acid methyl ester hydrochloride (Kotha et al.,Tetrahedron 2002, 58, 9203-9208). ₁H NMR (300 MHz, D₂O) δ 4.21 (t, 1H),δ 3.90 (s, 3H), δ 2.41 (t, 1H), δ 2.28 (m, 2H), δ 2.01 (m, 2H), δ 1.51(m, 6H) ppm; ₁₃C NMR (75 MHz, D₂O) δ 171.1, 86.4, 69.4, 53.7, 53.1,29.8, 27.5, 27.4, 23.8, 17.6 ppm; HRMS (ESI) calcd for C₁₀H₁₈NO₂ (M+)184.1332, found 184.1329.

2-Amino-dec-9-ynoic acid methyl ester hydrochloride was synthesizedusing, the same methods previously reported for the synthesis of2-Amino-pent-4-ynoic acid methyl ester hydrochloride (Kotha et al.,Tetrahedron 2002, 58, 9203-9208). ₁H NMR (300 MHz, D₂O) δ 4.16 (t, 1H),δ 3.86 (s, 3H), δ 2.36 (t, 1H), δ 2.21 (m, 2H), δ 1.98 (m, 2H), δ1.55-1.39 (m, 8H) ppm; ₁₃C NMR (75 MHz, D₂O) δ 171.2, 86.7, 69.3, 53.7,53.1, 29.8, 27.7, 27.7, 27.6, 24.1, 17.6 ppm; HRMS (ESI) calcd forC₁₁H₂₀NO₂ (M+) 198.1488, found 198.1488.

2-Amino-pent-4-ynoic acid methyl ester hydrochloride (2.91 g, 17.8 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (1.65 g, 59%) as ayellow oil (Olofson et al., Journal of Organic Chemistry 1997, 62, (23),7918-7919). ₁H NMR (300 MHz, CD₃OD) δ 6.30 (s, 1H), δ 5.02 (d, 2H), δ2.26 (t, 1H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 150.1, 127.2, 109.6, 83.6,69.8, 15.9 ppm; HRMS (ESI) calcd for C₆H₇N₃ (M+) 122.0712, found122.0713.

2-Amino-hex-5-ynoic acid methyl ester hydrochloride (2.53 g, 14.2 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (1.17 g, 48%) as a paleyellow oil (Olofson et al., Journal of Organic Chemistry 1997, 62, (23),7918-7919). ₁H NMR (300 MHz, CD₃OD) δ 6.52 (s, 1H), δ 2.61 (t, 2H), δ2.42 (m, 2H), δ 2.27 (t, 1H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 147.4,126.2, 109.4, 81.9, 69.9, 23.8, 17.4 ppm; HRMS (ESI) calcd for C₇H₁₀N₃(M+) 136.0869, found 136.0865.

2-Amino-hept-6-ynoic acid methyl ester hydrochloride (2.00 g, 10.4 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (1.75 g, 90%) as apale oil (Olofson et al., Journal of Organic Chemistry 1997, 62, (23),7918-7919). ₁H NMR (300 MHz, CDCl₃) δ 6.68 (bs, 2H), δ 6.24 (s, 1H), δ2.51 (t, 2H), δ 2.17 (t, 1H), δ 1.95 (s, 1H), δ 1.74 (m, 2H) ppm; ₁₃CNMR (75 MHz, CDCl₃) δ 148.3, 132.7, 111.6, 84.4, 69.1, 28.0, 26.0, 18.2ppm; HRMS (ESI) calcd for C₁₀H₁₆N₃ (M+) 150.1026, found 150.1029:

2-Amino-oct-7-ynoic acid methyl ester hydrochloride (2.90 g, 14.1 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-Hex-5-ynyl-1H-imidazol-2-ylamine hydrochloride (2.45 g, 87%) as a paleyellow solid (Olofson et al., Journal of Organic Chemistry 1997, 62,(23), 7918-7919). ₁H NMR (300 MHz, CD₃OD) δ 6.43 (s, 1H), δ 2.44 (t,2H), 2.14 (t, 1H), δ 2.12 (m, 2H), δ 1.64 (m, 2H), δ 1.47 (m, 2H) ppm;₁₃C NMR (75 MHz, CD₃OD) δ 147.3, 127.6, 108.5, 83.4, 68.7, 27.7, 27.1,23.8, 17.5 ppm; HRMS (ESI) calcd for C₉H₁₄N₃ (M+) 164.1182, found164.1182.

2-Amino-non-8-ynoic acid methyl ester hydrochloride (2.02 g, 9.20 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-Hept-6-ynyl-1H-imidazol-2-ylamine hydrochloride (1.04 g, 53%) as apale yellow solid (Olofson et al., Journal of Organic Chemistry 1997,62, (23), 7918-7919). ₁H NMR (300 MHz, CD₃OD) δ 6.17 (s, 1H), δ 2.19 (t,2H), δ 1.90 (t, 1H), δ 1.86 (m, 2H), δ 1.24-1.13 (m, 6H) ppm; ₁₃C NMR(75 MHz, CD₃OD) δ 147.5, 128.3, 108.8, 83.8, 65.5, 28.4, 28.3, 28.2,24.5, 17.8 ppm; HRMS (ESI) calcd for C₁₀H₁₆N₃ (M+) 178.1338, found178.1337.

2-Amino-dec-9-ynoic acid methyl ester hydrochloride (1.50 g, 6.42 mmol)was treated to an Akabori reduction followed by a cyanamide condensationemploying conditions previously reported to produce4-Oct-7-ynyl-1H-imidazol-2-ylamine hydrochloride (0.774 g, 53%) as apale yellow solid (Olofson et al., Journal of Organic Chemistry 1997,62, (23), 7918-7919). ₁H NMR (400 MHz, CD₃OD) δ 6.09 (s, 1H), δ 2.19 (t,2H), δ 1.95 (t, 1H), 1.93 (m, 2H), δ 1.39-1.11 (m, 8H) ppm; ₁₃C NMR (75MHz, CD₃OD) δ 148.5, 131.0, 110.1, 83.9, 68.3, 28.6, 28.5, 28.4, 28.3,25.7, 17.8 ppm; HRMS (ESI) calcd for C₁₁H₁₈N₃ (M+) 192.1495, found192.1495.

To a 50 mL round-bottomed flask equipped with a magnetic stirbar wasadded 1-H-1,2,3-triazole (0.192 g, 2.78 mmol) and DMF (10 mL) and thencooled to 0° C. while stirring. Then, sodium hydride (60% dispersion inmineral oil) (0.133 g, 3.33 mmol) is added to the reaction mixture andwas slowly allowed to warm to ambient temperature. Then, 1-iodo-4pentyne (0.647 g, 3.33 mmol) was added dropwise. The reaction mixturewas then heated to 80° C. and allowed to stir for 2.5 hours. Water (20mL) was then added to the reaction mixture and then extracted with ethylacetate (2×20 mL). The organic phase was dried with sodium sulfate andconcentrated de vacuo followed by a purification by columnchromatography (ethyl acetate/hexane) to produce1-Pent-4-ynyl-1H-[1,2,3]triazole (0.349 g, 93%) as a colorless oil. ₁HNMR (300 MHz, CDCl₃) δ 7.67 (s, 1H), δ 7.59 (s, 1H), δ 4.53 (t, 2H), δ2.20 (t, 2H), δ 2.17 (m, 2H), δ 2.04 (s, 1H) ppm; ₁₃C NMR (75 MHz,CDCl₃) δ 133.9, 123.9, 82.2, 70.4, 48.7, 28.9. 15.7 ppm; HRMS (ESI)calcd for C₇H₁₀N₃ (M+) 136.0869, found 136.0866.

General procedure for click reactions: The terminal alkyne (1.0 equiv.)was dissolved in a 1:1:1 mixture of tert-butyl alcohol, water andmethylene chloride (ca. 10 mL per 0.300 g of terminal alkyne). To thissolution, the appropriate azide (1.2 equiv.) was added while stirringvigorously at room temperature. Copper (II) sulfate pentahydrate (15 mol%) and sodium ascorbate (45 mol %) were then added sequentially to thesolution. Reaction mixtures were allowed to stir until completion viaTLC analysis (12-24 hrs). The solvents were then removed de vacuo inwhich the resulting residue was dissolved in methanol and purified byflash chromatography (10-20% ammonia saturated methanol: methylenechloride). The resulting fractions were evaporated under reducedpressure followed by a 24 hr high vacuum treatment to remove all ammoniatraces. Methanol saturated with HCl is then added to the purifiedproduct in which all volatiles are then removed under reduced pressure.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.127 g, 0.809 mmol)was reacted with (3-Azido-2-methyl-propenyl)-benzene (0.168 g, 0.971mmol) following the general procedure for click reactions outlined aboveto produce4-[1-(2-Methyl-3-phenyl-allyl)-1H[1,2,3]triazol-4-ylmethyl]-1H-imidazol-2-ylaminehydrochloride (0.244 g, 91%) of a pale yellow solid. ₁H NMR (300 MHz,D₂O) δ 7.94 (s, 1H), δ 7.40-7.35 (m, 5H), δ 6.56 (s, 1H), δ 5.10 (s,2H), δ 3.99 (s, 2H), δ 1.76 (s, 3H) ppm; ₁₃C δ 145.8, 138.1, 136.9,136.5, 136.4, 132.8, 128.3, 128.0, 127.6, 125.3, 123.4, 49.3, 23.8,23.4; HRMS (ESI) calcd for C₁₆H₁₈N₆ (M+) 295.1665, found 295.1665.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.095 g, 0.603 mmol)was reacted with benzyl azide (0.096 g, 0.723 mmol) following thegeneral procedure for click reactions outlined above to produce4-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethyl)-1H-imidazol 2-ylaminehydrochloride (0.151 g. 86%) of a pale yellow solid. ₁H NMR (300 MHz,D₂O) δ 7.79 (s, 1H), δ 7.42-7.35 (m, 5H), δ 6.43 (s, 1H), δ 5.58 (s,2H), δ 3.86 (s, 2H) ppm; ₁₃C δ 145.4, 136.6, 135.4, 128.8, 128.7, 126.9,126.8, 126.3, 124.1, 121.8, 109.6, 53.3, 24.1 ppm; HRMS (ESI) calcd forC₁₃H₁₆N₆O (M+) 254.1352, found 254.1352.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.101 g, 0.639 mmol)was reacted with 3-azidomethyl-furan (0.094 g, 0.767 mmol) following thegeneral procedure for click reactions outlined above to produce4-(1-Furan-3-ylmethyl-1H-[1,2,3]triazol-4-ylmethyl)-1H-imidazol-2-ylaminehydrochloride (0.077 g, 43%) of a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.12 (s, 1H), δ 7.60 (s, 1H), δ 7.38 (s, 1H), δ 6.53 (s, 1H), δ6.37 (s, 1H), δ 5.46 (s, 2H), δ 3.95 (s, 2H) ppm; ₁₃C NMR (75 MHz,CD₃OD) δ 146.1, 145.3, 144.1, 141.0, 123.3, 123.1, 110.3, 110.2, 109.9,51.3, 19.9 ppm; HRMS (ESI) calcd for C₁₁H₁₂N₆O (M+) 244.1145, found244.1145.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.096 g, 0.061 mmol)was reacted with 2-azidomethyl-furan (0.089 g, 0.729 mmol) following thegeneral procedure for click reactions outlined above to produce4-(1-Furan-2-ylmethyl-1H-[1,2,3]triazol-4-ylmethyl)-1H-imidazol-2-ylaminehydrochloride (0.078 g, 46%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.93 (s, 1H), δ 7.41 (s, 1H), 6.49 (s, 2H), δ 6.32 (s, 1H), δ5.56 (s, 2H), δ 3.89 (s, 2H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 146.2,146.1, 142.4, 141.5, 122.3, 122.2, 108.9, 109.2, 108.8, 51.6, 18,9 ppm;HRMS (ESI) calcd for C₁₁H₁₂N₆O (M+) 245.1145, found 245.1147.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.096 (0.061 mmol)was reacted with 3-azidomethyl thiophene (0.102 g, 0.732 mmol) followingthe general procedure for click reactions outlined above to produce4-(1-Thiophen-3-ylmethyl-1H-[1,2,3]triazol-4-ylmethyl)-1Himidazol-2-ylaminehydrochloride (0.079 g, 44%) of a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.18 (s, 1H), δ 7.44 (s, 1H), δ 7.30 (d, 1H), δ 6.98 (d, 1H), δ6.53 (s, 1H), δ 5.57 (s, 2H), δ 3.95 (s, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ145.7, 145.1, 143.7, 139.7, 129.8, 121.8, 111.5, 109.8, 109.2, 52.7,21.5 ppm; HRMS (ESI) calcd for C₁₁H₁₂N₆S (M+) 260.0919, found 260.0919.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.101 g, 0.641 mmolwas reacted with 3-(2-Azido-ethyl)-thiophene (0.118 g, 0.769 mmol)following the general procedure for click reactions outlined above toproduce 4-[1-(2-Thiophen-3-yl-ethyl)-1H[1,2,3]triazol-4-ylmethyl]-1H-imidazol-2-ylamine hydrochloride (0.119 g,60%) of a pale yellow solid. ₁H NMR (300 MHz, CD₃OD) δ 7.42 (s, 1H), δ7.19 (t, 1H), δ 6.90 (s, 1H), □ 6.78 (d, 1H), δ 6.09 (s, 1H), δ 4.47 (t,2H), δ 3.67 (s, 2H), δ 3.09 (t, 2H) ppm; ₁₃C; (75 MHz, CD₃OD) δ 151.2,145.7, 137.7, 130.5, 127.8, 125.8, 122.9, 121.9, 110.3, 50.798, 30.7,23.3 ppm; HRMS (ESI) calcd for C₁₂H₁₄N₆S (M+) 274.1001, found 274.1007.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.047 g, 0.295 mmol)was reacted with 2-azidomethyl-5,6-dimethyl-1H-benzimidazole (0.071 g,0.354 mmol) following the general procedure for click reactions outlinedabove to produce 4-[1-(5,6Dimethyl-1H-benzoimidazol-2-ylmethyl)-1H-[1,2,3]triazol-4-ylmethyl]-1H-imidazol-2-ylaminedihydrochloride (0.029 g, 25%) of a yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.09 (s, 1H), δ 7.45 (s, 2H), δ 6.52 (s, 1H), δ 6.08 (s, 2H), δ3.93 (s, 2H), δ 2.35 (s, 6H) ppm; ₁₃C (75 MHz, CD₃OD) δ 142.2, 136.9,136.6, 124.5, 124.3, 113.8, 113.4, 110.0, 100.4, 85.8, 80.6, 75.3, 74.1,45.0, 20.9, 19.28 ppm; HRMS (ESI) calcd for C₁₆H₁₈N₈ (M+) 323.1727,found 323.1734.

4-Prop-2-ynyl-1H-imidazol-2-ylamine hydrochloride (0.091 g, 0.576 mmol)was reacted with 2-azidomethyl-1H-benzimidazole, which was synthesizedusing previously reported methods (Hiales et al., Synthesis 1978, 4,313-315), (0.120 g,0.691 mmol) following the general procedure for clickreactions outlined above to produce4-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-[1,2,3]triazol-4-ylmethyl]1Himidazol-2-ylamine dihydrochloride (0.125 g, 59%) of a yellow solid.₁H NMR (300 MHz, CD₃OD) δ 8.01 (s, 1H), δ 7.58 (d, 2H), δ 7.31 (t, 2H),δ 6.44 (s, 1H), δ 5.98 (s, 2H) δ 3.84 (s, 2H) ppm; ₁₃C (75 MHz. CD₃OD) δ135.6, 124.7, 123.7, 123.5, 122.8, 112.8, 112.3, 108.4, 83.6, 78.9,74.0, 73.2, 44.2, 19.3 ppm; HRMS (ESI) calcd for C₁₄H₁₄N₈ (M+) 295.1414,found 295.1420.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.0735 g, 0.428 mmol)was reacted with (3-azido-propyl) benzene, which was synthesized usingpreviously reported methods (Suenaga et al., Tetrahedron Letters 2003,44, 5799-5801), (0.083 g, 0.514 mmol) following the general procedurefor click reactions outlined above to produce4-{2-[1-(3-Phenyl-propyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminehydrochloride (0.051 g, 36%) of a pale yellow oil. ₁H NMR (300 MHz,CD₃OD) δ 7.87 (s, 1H), δ 7.32-7.22 (m, 5H), δ 6.54 (s, 1H), δ 4.31 (t,2H), δ 3.05 (t, 2H), δ 2.93 (t, 2H), δ 2.67 (t, 2H), δ 2.23 (m, 2H) ppm;₁₃C (75 MHz CD₃OD) δ 153.3, 146.6, 140.4, 134.3, 128.8, 128.7, 128.6,126.6, 121.5, 67.5, 53.9. 32.8, 32.9, 29.5 ppm; HRMS (ESI) calcd forC₁₆H₂₀N₆ (M+) 296.1822, found 296.1828.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.062 g, 0.362) wasreacted with (3-Azido-2-methyl-propenyl)-benzene (0.075 g, 0.434 mmol)following, the general procedure for click reactions outlined above toproduce4-{2-[1-(2-Methyl-3-phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminehydrochloride (0.054 g, 43%) of a pale yellow oil. ₁H NMR (300 MHz,CD₃OD) δ 8.39 (s, 1H), δ 7.12-7.07 (m, 5H), δ 6.54 (s, 1H), δ 6.36 (s,1H), δ 5.09 (s, 2H), δ 3.01 (t, 2H), δ 2.76 (t, 2H), δ 1.60 (s, 3H) ppm;₁₃C; 147.7, 143.1, 136.3, 132.7, 129.9, 128.9, 128.6, 128.5, 128.2,127.4, 127.1, 124.9, 109.9, 61.2, 23.0, 22.3, 14.7 ppm; HRMS (ESI) calcdfor C₁₆H₂₀N₆ (M+) 308.1749, found 308.1742.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.068 g, 0.399 mmol)was reacted with 2-azidomethyl furan (0.059 g, 0.478 mmol) following thegeneral procedure for click reactions outlined above to produce4-[2-(1-Furan-2-ylmethyl-1H-[1,2,3]triazol-4-yl)-ethyl]-1H-imidazol-2-ylaminehydrochloride (0.085 g, 72%) of a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.06 (s, 1H), δ 7.53 (s, 1H), δ 6.59 (t, 1H), δ 6.49 (s, 1H), δ6.44 (dd, 1H), δ 3.05 (t, 2H), δ 2.89 (t, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ156.4, 154.9, 147.5, 144.1, 126.0, 125.1, 123.8, 110.7, 109.3, 69.8,23.8, 17.4 ppm; HRMS (ESI) calcd for C₁₂H₁₄N₆O (M+) 259.1301, found259.1305.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.078 g, 0.45 mmol)was reacted with 3-(2-Azido-ethyl)-thiophene (0.083 g, 0.543 mmol)following the general procedure for click reactions outlined above toproduce4-{2-[1-(2-Thiophen-3-yl-ethyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminehydrochloride (0.069 g, 47%) of a pale yellow oil. ₁H NMR (300 MHz,CD₃OD) δ 7.33 (s, 1H), δ 7.19 (dd, 1H), δ 6.85 (d, 1H), δ 6.72 (d, 1H),δ 6.06 (s, 1H), δ 4.45 (t, 2H), δ 3.08 (t, 2H), δ 2.79 (t, 2H), δ 2.59(t, 2H), ppm ₁₃C (75 MHz, CD₃OD) δ 149.3, 147.0, 137.7, 132.1, 127.7,125.8, 122.4, 121.9, 110.6, 50.8, 30.7, 26.6, 24.8 ppm; HRMS (ESI) calcdfor C₁₃H₁₇N₆S (M+) 289.1229, found 289.1231.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.066 g, 0.383 mmol)was reacted with (3-azido-propenyl)-benzene, which was synthesized usingpreviously reported methods (Rad et al., Tetrahedron Letters 2007, 48,3445-3449), (0.079 g, 0.460 mmol) following the general procedure forclick reactions outlined above to produce4-{2-[1-(3-Phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminehydrochloride (0.049 g, 39%) of a pale yellow oil. ₁H NMR (300 MHz,CD₃OD) δ 8.19 (s, 1H), δ 7.44 (d, 2H), δ 7.29 (m, 3H), δ 6.73 (d, 1H), δ6.53 (s, 1H), δ 6.42 (m, 2H), δ 5.24 (d, 2H), δ 3.07 (t, 2H), δ 2.88 (t,2H) ppm; ₁₃C 148.6, 145.3, 139.4, 139.2, 129.8, 129.7, 129.6, 128.5,128.4, 127.6, 54.6, 47.3. 45.9, 26.3, 22.6 ppm; HRMS (ESI) calcd forC₁₆H₁₉N₆ (M+) 295.1665, found 295.1670.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.066 g, 0.384 mmol)was reacted with 3-azidomethyl-furan (0.057 g, 0.461 mmol) following thegeneral procedure for click reactions outlined above to produce4-[2-(1-Furan-3-ylmethyl-1H-[1,2,3]triazol-4-yl)-ethyl]-1H-imidazol-2-ylaminehydrochloride (0.061 g, 54%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.70 (s, 1H), δ 7.61 (s, 1H), δ 7.46 (s, 1H), δ 6.42 (s, 1H), δ6.38 (s, 1H), δ 5.41 (s, 2H), δ 2.95 (t, 2H), δ 2.83 (t, 2H) ppm; ₁₃C(75 MHz, CD₃OD) δ 146.3, 144.2, 141.6, 141.5, 126.5, 122.3, 120.2,109.9, 109.1, 44.8, 24.2, 23.9 ppm; HRMS (ESI) calcd for C₁₂H₁₄N₆O (M+)259.1301, found 259.1306.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.073 g, 0.423 mmol)was reacted with benzyl azide (0.068 g, 0.509 mmol) following thegeneral procedure for click reactions outlined above to produce4-[2-(1-Benzyl-1H-[1,2,3]triazol-4-yl)-ethyl]-1H-imidazol-2-ylaminehydrochloride (0.059 g, 46%) as a pale yellow oil. ₁H NMR (300 MHz,CD₃OD) δ 7.83 (d, 1H), δ 7.37-7.24 (m, 5H), δ 6.44 (d, 1H), δ 5.54 (d,2H), δ 2.96 (m, 2H), δ 2.83 (m, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ 163.7,147.3, 146.4, 135.7, 128.8, 128.4, 127.9, 127.8, 126.5, 122.6, 109.1,53.7, 24.1, 23.9 ppm; HRMS (ESI) calcd for C₁₄H₁₆N₆ (M+) 269.1515, found269.1513.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.073 g, 0.429 mmol)was reacted with 3-azidomethyl-indole (0.089 g, 0.515 mmol) followingthe general procedure for click reactions outlined above to produce4-{2-[1-(1H-Indol-3-ylmethyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1Himidazol-2-ylaminehydrochloride (0.086 g, 58%) as a yellow oil. ₁H NMR (300 MHz, CD₃OD) δ8.11 (s, 1H), δ 7.84 (m, 2H), δ 7.41 (m, 2H), δ 7.06 (d, 1H), δ 5.66 (s,2H), δ 3.04 (t, 2H), δ 2.85 (t, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ 147.5,144.9, 144.8, 134.7, 131.9, 127.2, 127.1, 127.1, 125.8, 125.3, 124.4,109.5, 49.9, 23.6, 23.2 ppm; HRMS (ESI) calcd for C₁₇H₁₉N₇ (M+)321.1701, found 321.1704.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.061 g, 0.361 mmol)was reacted with 2-azidomethyl-1-H-benzimidazole (0.075 g, 0.433 mmol)following the general procedure for click reactions outlined above toproduce4-{2-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminedihydrochloride (0.066 g, 48%) of a yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.05 (s, 1H), δ 7.68 (m. 2H), δ 7.48 (m, 2H), δ 6.38 (s, 1H), δ6.15 (s, 2H′), δ 2.90 (t, 2H), δ 2.76 (t, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ146.9, 146.8, 131.3, 127.0, 126.4, 124.1, 114.1, 109.2, 44.7, 24.0, 23.9ppm; HRMS (ESI) calcd for C₁₅H₁₇N₈ (M+) 309.1570, found 309.1572.

4-But-3-ynyl-1H-imidazol-2-ylamine hydrochloride (0.0734 g, 0.432 mmol)was reacted with 2-azidomethyl-5,6-dimethyl-1H-benzimidazole (0.104 g,0.518 mmol) following the general procedure for click reactions outlinedabove to produce4-{2-[1-(5,6-Dimethyl-1Hbenzoimidazol-2-ylmethyl)-1H-[1,2,3]triazol-4-yl]-ethyl}-1H-imidazol-2-ylaminedihydrochloride (0.104 g, 59%) of a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.70 (s, 1H), δ 7.19 (s, 2H), δ 6.23 (s, 1H), δ 5.66 (s, 2H), δ2.85 (t, 2H), δ 2.68 (t, 2H), □ 2.21 (s, 6H) ppm; ₁₃C (75 MHz, CD₃OD) δ148.2, 147.0, 146.9, 132.3, 128.9, 122.8, 120.0, 115.1, 109.7, 100.4,25.1, 24.4, 19.2 ppm; HRMS (ESI) calcd for C₁₇H₂₀N₈ (M+) 337.1883, found337.1886.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.050 g, 0.269 mmol)was reacted with (3-azido-propyl) benzene (0.044 g, 0.273 mmol)following the general procedure for click reactions outlined above toproduce4-{3-[1-(3-Phenyl-propyl)-1H-[1,2,3]triazol-4-yl]-propyl}-1H-imidazol-2-ylaminehydrochloride (0.0318 g, 34%) as a pale yellow solid. ₁H NMR (300 MHz,DMSO) δ 7.91 (s, 1H), δ 7.29-7.17 (m, 5H), δ 6.62 (s, 2H), δ 6.57 (s,1H), δ 4.29 (t, 2H), δ 2.59 (t, 2H), δ 2.53 (t, 2H), δ 2.43 (t, 2H) δ2.09 (m, 2H), δ 1.83 (m, 2H) ppm; ₁₃C NMR (75 MHz, DMSO) δ 163.6, 156.2,155.1, 147.4, 146.9, 141.4, 129.1, 127.1, 126.7, 122.6, 109.4, 49.4,32.6, 32.0, 28.1, 24.9, 24.2 ppm; HRMS (ESI) calcd for C₁₇H₂₂N₆ (M+)310.1978, found 310.1977.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.063 g, 0.340 mmol)was reacted with 3-azidomethyl-furan (0.050 g, 0.406 mmol) following,the general procedure for click reactions outlined above to produce4-[3-(1-Furan-3-ylmethyl-1H-[1,2,3]triazol-4-yl)-propyl]-1Himidazol-2-ylaminehydrochloride (0.061 g, 58%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.70 (s, 1H), δ 7.56 (s, 1H), δ 7.41 (s, 1H), δ 6.44 (s, 1H), δ6.35 (s, 1H), δ 5.35 (s, 2H), δ 2.65 (t, 2H), δ 2.45 (t, 2H), δ 1.86 (m,2H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 147.3, 147.3, 144.2, 141.6, 127.2,122.1, 120.2, 109.9, 108.8, 44.7, 27.8, 24.2, 23.6 ppms; HRMS (ESI)calcd for C₁₃H₁₆N₆O (M+) 272.1458, found 272.1462.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.093 g, 0.500 mmol)was reacted with 2-azidomethyl-furan (0.074 g, 0.601 mmol) following thegeneral procedure for click reactions outlined above to produce4-[3-(1-Furan-2-ylmethyl-1H-[1,2,3]triazol-4-yl)-propyl]-1Himidazol-2-ylaminehydrochloride (0.075, 50%) as a pale yellow solid. ₁H NMR (300 MHz,DMSO) δ 7.85 (s, 1H), δ 7.65 (s, 1H), δ 6.70 (s, 2H), δ 6.64 (s, 1H), δ6.52 (t, 1H), δ 6.46 (s, 1H), δ 5.58 (s, 2H), δ 2.61 (t, 2H), δ 2.41 (t,2H), δ 1.82 (m, 2H) ppm; ₁₃C NMR (75 MHz, DMSO) δ 163.6, 149.4, 147.9,147.4, 144.3, 128.5, 122.6, 111,5, 110.3, 109.9, 46.3, 28.4, 24.9 ppm;HRMS (ESI) calcd for C₁₃H₁₆N₆O (M+) 272.1458, found 272.1460.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.090 g, 0.486 mmol)was reacted with 3-Azidomethyl-thiophene (0.081 g, 0.582 mmol) followingthe general procedure for click reactions outlined above to produce4-[3-(1-Thiophen-3-ylmethyl-1H-[1,2,3]triazol-4-yl)-propyl]-1H-imidazol-2-ylaminehydrochloride (0.0727 g, 46%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.61 (s, 1H), δ 7.24 (s, 1H), δ 7.23 (d, 1H), δ 6.87 (d, 1H), δ6.29 (s, 1H), δ 2.54 (t, 2H), 2.33 (t, 2H), δ 1.75 (m, 2H) ppm; ₁₃C NMR(75 MHz, CD₃OD) δ 147.6, 147.4, 147.3, 136.1, 127.9, 127.0, 126.9,124.2, 122.2, 109.1, 53.1, 27.9, 24.3; HRMS (ESI) calcd for C₁H₁₆N₆S(M+) 289.1229, found 289.1234.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.096 g, 0.517 mmol)was reacted with (3-Azido-2-methyl-propenyl)-benzene (0.110 g, 0.635mmol) following the general procedure for click reactions outlined aboveto produce5-{3-[1-(2-Methyl-3-phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-propyl}-1H-imidazol-2-ylaminehydrochloride (0.076, 41%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.65 (s, 1H), δ 7.14-7.04 (m, 5H), δ 6.35 (s, 1H), δ 6.28 (s,1H), δ 4.94 (s, 2H), δ 2.57 (t, 2H), δ 2.34 (t, 2H), δ 1.75 (m, 2H), δ1.57 (s, 3H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 147.5, 136.9, 132.5, 129.7,128.8, 128.6, 128.4, 128.3, 128.2, 126.9, 122.5, 109.2, 58.1, 61.9,28.0, 24.3, 24.3, 24.1, 14.6 ppm; HRMS (ESI) calcd for C₁₈H₂₂N₆ (M+)323.1978, found 323.1984.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.081 g, 0.437 mmol)was reacted with benzyl azide (0.071 g, 0.533 mmol) following thegeneral procedure for click reactions outlined above to produce4-[3-(1-Benzyl-1H-[1,2,3]triazol-4-yl)-propyl]-1H-imidazol-2-ylaminehydrochloride (0.073 g, 53%) as a pale yellow solid. ₁H NMR (300 MHz,DMSO) δ 7.93 (s, 1H), δ 7.37-7.27 (m, 5H), δ 6.63 (s, 2H), δ 6.44 (s,1H), δ 2.61 (t, 2H), δ 2.40 (t, 2H), δ 1.82 (m, 2H) ppm; ₁₃C NMR (75MHz, DMSO) δ 163.5, 148.1, 147.4, 135.9, 129.4, 128.7, 128.5, 128.4,122.8, 122.8, 115.9, 109.9, 53.3, 28.5, 25.0; HRMS (ESI) calcd forC₁₅H₁₈N₆ (M+) 282.1665, found 282.1674.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.090 g, 0.485 mmol)was reacted with 3-(2-Azido-ethyl)-thiophene (0.089 g, 0.581 mmol)following the general procedure for click reactions outlined above toproduce4-{3-[1-(2-Thiophen-3-yl-ethyl)-1H-[1,2,3]triazol-4-yl]-propyl}-1H-imidazol-2-ylaminehydrochloride (0.067 g, 41%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 7.42 (s, 1H), δ 7.12 (d, 1H), δ 6.83 (s, 1H), δ 6.70 (d, 1H), δ6.29 (s, 1H), δ 4.41 (t, 2H), δ 3.04 (t, 2H), δ 2.50 (t, 2H), δ 2.29 (t,2H), δ 1.72 (m, 2H) ppm; ₁₃C NMR (75 MHz, CD₃OD) δ 146.8, 146.8, 137.7,127.8, 127.6, 125.7, 122.6, 121.9, 109.0, 50.7, 30.7, 27.9, 23.7 ppm;HRMS (ESI) calcd for C₁₄H₁₈N₆S (M+) 302.1313, found 302.1317.

4-Pent-4-ynyl-1H-imidazol-2-ylamine hydrochloride (0.115 g, 0.620 mmol)was reacted with (3-azido-propenyl)-benzene (0.119 g, 0.748 mmol)following, the general procedure for click reactions outlined above toproduce4-{3-[1-(3-Phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-propyl}-1Himidazol-2-ylamine hydrochloride (0.082 g, 43%) as a pale yellow solid. ₁H NMR(300 MHz, CDCl₃) δ 7.34-7.24 (m, 6H), δ 6.67 (d, 1H), δ 6.34 (q, 1H), δ6.25 (s, 1H), δ 5.08 (d, 2H), δ 2.72 (t, 2H), δ 2.47 (t, 2H), δ 1.91 (m,2H) ppm; ₁₃C (75 MHz, CD₃OD) 149.1, 137.9, 133.5, 129.5, 128.9, 128.7,128.3, 128.2, 127.7, 126.8, 54.8, 48.9, 31.3, 29.6, 27.5 ppm ; HRMS(ESI) calcd for C₁₇H₂₁N₆ (M+) 308.1822, found 308.1821.

4-Hex-5-ynyl-1H-imidazol-2-ylamine hydrochloride (0.089 g, 0.4.47 mmol)was reacted with (3-Azido-2-methyl-propenyl)-benzene (0.085 g, 0.491mmol) following the general procedure for click reactions outlined aboveto produce4-{4-[1-(2-Methyl-3-phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-butyl}-1H-imidazol-2-ylamine(0.132 g, 79%) as a pale yellow solid. ₁H NMR (300 MHz, CD₃OD) δ 8.36(s, 1H), 7.03 (m, 5H), 6.49 (s, 1H), 6.25 (s, 1H), 5.05 (s, 2H), δ 2.67(t, 2H), δ 2.73 (t, 2H), δ 1.56 (s, 3H), δ 1.42 (m, 4H) ppm; ₁₃C (75MHz, CD₃OD) δ 147.3, 144.7, 136.4, 132.7, 129.9, 128.9, 128.6, 128.5,128.3, 127.5, 127.2, 126.9, 108.7, 61.2, 27.4, 27.3, 23.8, 22.8, 14.8ppm; HRMS (ESI) calcd for C₁₉H₂₄N₆ (M+) 336.2135, found 336.2134.

4-Hept-6-ynyl-1H-imidazol-2-ylamine hydrochloride (0.060 g, 0.281 mmol)was reacted with (3-Azido-2-methyl-propenyl)-benzene (0.058 g, 0.336mmol) following the general procedure for click reactions outlined aboveto produce4-{5-[1-(2-Methyl-3-phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-pentyl}-1H-imidazol-2-ylaminehydrochloride (0.064 g, 65%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.23 (s, 1H), δ 6.93-6.83 (m, 5H), δ 6.38 (s, 1H), δ 6.08 (s,1H), δ 4.93 (s, 2H), δ 2.51 (t, 2H), δ 2.09 (t, 2H), δ 1.43 (s, 3H), δ1.41 (m, 2H), δ 1.25 (m, 2H), δ 1.05 (m, 2H) ppm; ₁₃C (75 MHz, CD₃OD) δ147.7, 144.8, 136.3, 132.8, 129.8, 128.9, 128.6, 128.5, 128.2, 127.6,127.5, 127.0, 108.5, 61.3, 28.0, 27.6, 27.5, 24.0, 22.9, 14.7 ppm; HRMS(ESI) calcd for C₂₀H₂₇N₆ (M+) 351.2291, found 351.2291.

4-Oct-7-ynyl-1H-imidazol-2-ylamine hydrochloride (0.098 g, 0.568 mmol)was reacted with (3-Azido-2-methyl-propenyl)-benzene (0.118 g, 0.681mmol) following the general procedure for click reactions outlined aboveto produce4-{6-[1-(2-Methyl-3-phenyl-allyl)-1H-[1,2,3]triazol-4-yl]-hexyl}-1H-imidazol-2-ylaminehydrochloride (0.147 g, 85%) as a pale yellow solid. ₁H NMR (300 MHz,CD₃OD) δ 8.42 (s, 1H), δ 7.25-7.15 (m, 5H), δ 6.65 (s, 1H), δ 6.36 (s,1H), δ 5.23 (s, 2H), δ 2.78 (t, 2H), δ 2.38 (t, 2H), δ 1.74 (s, 3H), δ1.64 (m, 2H), δ 1.51 (m, 2H), δ 1.33 (m, 4H) ppm; ₁₃C (75 MHz, CD₃OD) δ147.5, 136.3, 132.9, 132.8, 129.9, 128.9, 128.6, 128.5, 128.3, 127.7;HRMS (ESI) calcd for C₂₁H₂₉N₆ (M+) 365.2448, found 365.2448.

1-Pent-4-ynyl-1H-[1,2,3]triazole (0.100 g, 0.739 mmol) was reacted with(3-Azido-2-methylpropenyl)-benzene (0.154 g, 0.889 mmol) following thegeneral procedure for click reactions outlined above to produce1-(2-Methyl-3-phenyl-allyl)-4-(3-[1,2,3]triazol-1-yl-propyl)-1H-[1,2,3]triazole(0.227 g, Quantitative) as a white solid. ₁H NMR (300 MHz, DMSO) δ 7.91(s, 1H), δ 7.77 (s, 2H), δ 7.40-7.25 (m, 5H), δ 6.47 (s, 1H), δ 5.05 (s,2H), δ 4.48 (t, 2H), δ 2.62 (t, 2H), δ 2.50 (t, 2H), δ 2.21 (m, 2H), δ1.74 (s, 3H) ppm; ₁₃C (75 MHz, DMSO) δ 146.4, 137.1, 134.8, 133.6,132.8, 129.4, 129.3, 129.2, 128.9, 127.6, 123.0, 57.9, 54.0, 32.9, 29.6,22.7, 16.2 ppm; HRMS (ESI) calcd for C₁₇H₂₁N₆ (M+) 309.1822, found309.1821.

Example 2 Activity Testing of 2-AIT Library Members

A standard crystal violet reporter assay is employed to assess theeffect of compounds from the 2-amino on the formation of biofilms. Amongothers, the following strains are tested:

Xanthomonas Xccl

Xanthomonas Xcv.135

Xanthomonas Xcv5

Xanthomonas Xccp

Xanthomonas Xcp60

Xanthomonas Xcp25

Ralstonia solanacearum K66

Xanthomonas is a Gram-negative rod-shaped bacterium that is a commonplant pathogen. Xanthomonas bacteria grow almost exclusively in plants.Xanthomonas species testing includes X. vesicatoria (crop=tomato), X.euvesicatoria (crop=pepper), X. campestris (crop=crucifers, particularlycabbage), X. zinniae (crop=zinnia), and X. fragariae (crop=strawberry).Ralstonia solanacearum is a Gram-negative bacterium that is found insoil.

Bacteria are allowed to form biofilms in a multi-well plate in theabsence or presence of one or more compounds. Planktonic (or freegrowing) bacteria are then removed, wells washed vigorously, and crystalviolet added. Crystal violet stains the remaining bacteria which,following ethanol solubilization, is quantitated by spectrophotometry(A₅₄₀). Time-dependent and concentration-dependent analysis of eachcompound are performed.

Example 3 Activity Testing of 2-AIT Library Members on Xanthomonas

Biofilm formation on PVC microtiter wells was accomplished usingXanthomonas strains Xcv 135 (known to infect peppers and tomatoes) andXcv 5 (known to infect tomatoes but not peppers) as models. The StartingOptical Density (OD at 600 nm) for biofilm attachment assay was 0.55,the temperature for this assay was 28° C., the duration of incubationwas 6 hours under, and the assay was static.

Biofilm inhibition results are as follows for screens with Xcv 135. TheXcv 5 strain is tested in the same manner.

Compound Screened % Inhibition at 20 μM (vs. Xcv 135) Formula(II)(a)(5)(D) 86% Formula (II)(a)(6)(D) 85% Formula (II)(i)(a)(2)(J)  0%

Example 4 Activity Testing in Pepper Plants Inoculated with Xanthomonaseuvesicatoria (Bacterial Spot)

To test the effects of the triazole derivatives for plant biofilminhibition activity, the compound of Formula (II)(a)(5)(D) was used asan exemplary compound (the “biofilm inhibitor/disperser” or “BFI” in thetext hereinafter of Example 4).

The compound was evaluated under field conditions to determine whetherit controls or enhances control of bacterial spot (caused by thebacterium Xanthomonas euvesicatoria) of pepper when applied alone or intank-mixtures with a copper (Kocide 3000), an antibiotic (GWN-9350,gentamicin), or a putative plant defense activator (Prophyt). Tests wereperformed April-July 2008 at the North Carolina Agricultural ResearchService Sandhills Research Station, Montgomery County.

EXPERIMENTAL DESIGN and TREATMENT APPLICATIONS: Each treatment consistedof two 7-plant rows running east-west replicated in a four-blockcompletely randomized design. Each 7-plant row was 10.5 ft×2 ft. Thisarea was used to calculate the quantity of spray material extrapolatedfor a per acre basis. Plants of bell pepper cultivar ‘X3R-Camelot’ weretransplanted to the field on Apr. 24, 2008. On May 6, two plants in thesouth row of each plot of each treatment were inoculated with asuspension of copper-resistant strains of the bacterial pathogen. Theseplants were destined to serve as the inoculum source for each plot. Eachof the spray test materials was mixed in 1.5 liters of water and appliedusing a backpack sprayer by making a single pass on each side of theplant row. Treatments were applied weekly starting immediately after theplants had been inoculated May 6 followed by 7 additional weekly spraysfor a total of 8 applications through June 24.

DATA: Ratings of foliar disease were started May 22, when symptoms wereobserved on the inoculated plants and continued weekly through June 25.Disease was most severe on the inoculated plants and then spread to thenon-inoculated plants. Data from these two groups (inoculated plants andthe non-inoculated) were evaluated separately. The results are expressedas disease progress over time using the calculated Area Under theDisease Progress Curve (AUDPC). Two fruit harvests were done; July 1 and8. Because there had been plant loss in some plots, the number of plantsper plot was counted and yields (number of fruit and weight) werecalculated and are reported on a per plant basis per treatment. Resultsare presented in Table 2 below.

TABLE 2 Mean AUDPC Mean Mean number Mean fruit Treatment & rate/acre(based on for inoculated AUDPC for pepper yield 100 gal water/acre)plants* entire plot* fruit/plant (lb)/plant 1-NT Check 162 a** 45 a**6.0 ab** 1.85 ab** 2-Kocide 3000 (30% MCE) 123 b 37 ab 6.5 ab 1.86 ab1.25 lb 3-BFI 0.467 oz (35 mg/L) 113 b 42 a 4.8 b 1.46 b 4-GWN-9350(10%) 3.5 lb +  74 c 15 c 8.6 a 2.52 a GWN-65 1.0 pt 5-ProPhyt 5.0 pt114 b 37 ab 6.5 ab 2.06 ab 6-ProPhyt 5.0 pt +  64 c 25 bc 6.3 ab 1.74 bBFI 0.467 oz (35 mg/L) 7-GWN-9350 + GWN-65 1.0  41 c 12 c 8.3 a 2.51 apt + BFI 0.467 oz (35 mg/L) 8-Kocide 3000 1.25 lb +  62 c 16 c 8.6 a2.54 a BFI 0.467 oz (35 mg/L) L.S.D. α = 0.05  34 16 2.6 0.76 andprobability of > treatment F   0.0001  0.0006 0.0466 0.0483 value *0-9rating scale with 0 = no disease, 1 = at least 1 diseased leaf, 2 = 1-5%foliage diseased or defoliated, 3 = 6-10%, 4 = 11-15%, 5 = 16-25%, 6 =26-50%, 7 = 51-75%, 8 = 76-99%, and 9 = 100% leaves diseased or plantcompletely defoliated. **Means within a column followed by the sameletter do not differ significantly, L.S.D. α = 0.05.

Example 5 Activity Testing in Fungus

The compound of Formula (II)(a)(5)(D) was used as an exemplary compoundto evaluate the ability of 2-AIT compounds to inhibit the formation ofCandida albicans biofilms.

It was screened at 100 μM for its ability to inhibit to the formation ofC. albicans biofilms using a crystal violet reporter assay. Briefly,biofilms were allowed to form for 24 hours in a 96-well microtiter platein the absence or presence of 100 μM of the compound. The wells weresubsequently washed thoroughly with water to remove free-floating andloosely adherent fungus, and then treated with crystal violet. Crystalviolet stains the remaining surface attached fungus (i.e. the biofilm),which following solublization, can be quantified by spectrophotometry(A₅₄₀).

From this initial screen, we determined that the exemplary compound wasable to inhibit C. albicans formation by 12% at 100 μM. Follow up growthcurves at 100 μM demonstrated that this anti-biofilm activity wasnon-fungicidal (data not shown).

With this initial success of inhibiting fungal biofilms with a 2-AIderivative, we asked the question whether analogue synthesis coulddeliver alternative 2-AIT derivatives with enhanced anti-biofilmactivity in the context of fungal biofilms. Previous work in our lab hasdemonstrated that 2-AI-based inhibitors of biofilms can be sub-dividedinto three separate sections: 1) the 2-AI head, 2) the linker region,and 3) the tail region. Structure activity relationship (SAR) dataindicates that selectivity and activity can be tuned/enhanced bymodification of the tail region.

Based upon this data, we synthesized a new pilot library of 2-AIderivatives for anti-biofilm testing in which diversity could be rapidlyassembled via substituents off the triazole ring through commerciallyavailable carboxylic acids.

The synthetic approach to this library is outlined in Scheme 2. In ourprevious synthesis of 2-AIT conjugates, we employed the alkyne-derived2-AI as a precursor to the Cu¹-mediated [3+2] alkyne/azide cycloaddition(click reaction). Although this reaction worked well, purification ofthe resulting product was cumbersome due to the use of copious amountsof ammonia saturated methanol for column chromatography. Therefore, wedecided to revise the route by employing a boc-protected 2-AI alkynethat would allow more traditional means of purification (i.e.methanol/dichloromethane columns). The boc-protected scaffold wassynthesized from 7-octynoic acid by treatment with oxayl chloridefollowed by diazomethane and quenching the resulting α-diazo ketone withHBr to generate the intermediate α-bromo ketone. Cyclization withboc-guanidine then delivered the target 2-AI alkyne 5.

Once 5 had been synthesized, we assembled a diverse array of azidoamides to employ in the click reaction to create our pilot library of2-AIT conjugates. Briefly, 2-bromo-ethylamine was treated with sodiumazide to deliver 2-azido-ethylamine, which following acylation (via therespective acid chloride) generated the azido amides for elaborationinto the 2-AIT pilot library. Each azido amide was then subjected to theclick reaction with the 2-AI 5. Boc-deprotection (TFA/CH₂Cl₂) followedby counterion exchange (trifluoroacetate for chloride) delivered thetarget 2-AIT library for anti-biofilm screening.

Each member of the pilot library was assayed at 100 μM for its abilityto inhibit the formation of C. albicans biofilms using the crystalviolet reporter assay. From this assay, 2-AIT derivatives 7f and 7m weredetermined to be the most potent. Subsequent dose response studiesrevealed that 7f had an IC₅₀ of 2.9 μM while 7m had an IC₅₀ of 3.3 μM(Table 3). Growth curve and colony count analysis of 7f and 7m atrespective IC₅₀ values demonstrated their antibiofilm activity to benon-fungicidal (data not shown).

Next, we addressed whether 7f and 7m could disperse pre-formed C.albicans biofilms. C. albicans was allowed to establish biofilms in96-well microtiter plate for 24 hours. Plates were then washed to removeany free floating or loosely adherent fungus. The appropriate 2-AIT (7fand 7m) was then added to each well at 75 μM and the plate was allowedto incubate at 37° C. for 24 hours. Wells were then washed with waterand stained with CV to quantify any remaining biofilms. In comparison tobiofilms treated with media only, compound 7f dispersed 56% while 7mdispersed 62% of the pre-formed biofilm. Once we had established thatboth compounds could disperse pre-formed biofilms, we quantified thiseffect by determining 7f and 7m's EC₅₀ value against pre-formed C.albicans biofilms. Here, EC₅₀ is defined as the concentration at whichthe compound will disperse 50% of a pre-formed biofilm. Dose responsestudies revealed EC₅₀'s of 37.2 μM and 24.7 μM for 7f and 7mrespectively (Table 1). From a medical perspective, molecules thatsimply inhibit the formation of a biofilm could be used in aprophylactic sense; however, given that a majority of patients alreadyhave an established biofilm infection when they seek medicalintervention, molecules that are effective against a pre-formed biofilmare more clinically significant.

Once we had established that these next generation 2-AIT conjugates hadthe ability to inhibit and disperse C. albicans biofilms, we addressedwhether members of this library would also inhibit and disperse biofilmsfrom Cryptococcus neoformans, an opportunistic fungal strain known toinfect immunosuppressed patients, especially those with HIV infections.Initial screening of our library showed that 7e and 7m had potentanti-biofilm activity against C. neoformans. Follow up dose responsestudies revealed IC₅₀'s of 1.3 μM and 8.0 μM (Table 3). Comparison offungal growth in the presence or absence of either compound indicatedthat each compound was not fungicidal. Unfortunately, neither of thesecompounds was able to disperse pre-formed C. neoformans biofilms at theconcentrations tested.

TABLE 3 Fungal biofilm inhibition and dispersion. Compound IC₅₀ (μM)EC₅₀ (μM) C. albicans 7f 2.9 ± 0.7  37.2 ± 5.7 7m 3.3 ± 1.6  24.7 ± 4.5S. cerevisiae 7g 2.7 ± 0.1 207.4 ± 7.3 7h 50.4 ± 2.2  353.7 ± 7.3 7j130.6 ± 16.9  >400 C. neoformans 7e 1.3 ± 0.3 — 7m 8.0 ± 3.4 —

Synthesis: All reagents used for chemical synthesis were purchased fromcommercially available sources and used without further purification.Chromatography was performed using 60 Å mesh standard grade silica gelfrom Sorbtech. NMR solvents were obtained from Cambridge Isotope Labsand used as is. ¹H NMR (300 MHz or 400 MHz) and ¹³C NMR (75 MHz or 100MHz) spectra were recorded at 25° C. on Varian Mercury spectrometers.Chemical shifts (δ) are given in ppm relative to tetramethylsilane orthe respective NMR solvent; coupling constants (J) are in hertz (Hz).Abbreviations used are s=singlet, bs=broad singlet, d=doublet,dd=doublet of doublets, t=triplet, dt=doublet of triplets, bt=broadtriplet, qt=quartet, m=multiplet, bm=broad multiplet and br=broad.

N-(2-azidoethyl)tetradecanamide: To a 25 mL round-bottomed flaskequipped with a magnetic stir bar was added 2-azidoethanamine (0.102 g,1.18 mmol), DCM (5 mL) and then triethylamine (0.239 g, 2.37 mmol). Tothis reaction mixture, tetradecanoyl chloride (0.292 g, 1.18 mmol) wasadded dropwise and allowed to stir at room temperature for 24 hr. Then,the reaction mixture was concentrated de vacuo and then purified viasilica gel column chromatography (100% dichloromethane to 1:40methanol:dichloromethane) to give N-(2-azidoethyl)tetradecanamide (0.245g, 79% yield). NMR (300 MHz, CDCl₃) δ 5.86 (s, 1H), δ 3.42 (s, 4H), δ2.18 (t, J=7.8 Hz, 2H), δ 1.62 (m, 2H), δ 1.24 (m, 20H), δ 0.87 (t,J=3.9 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 173.7, 51.2, 39.1, 36.9,32.1, 29.9, 29.8, 29.7, 29.6, 29.5, 25.9, 22.9, 14.4 ppm; HRMS (ESI)calcd for C₁₆H₃₂N₄O (M+) 296.2576, found 296.2566.

N-(2-azidoethyl)octadec-9-enamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, octadec-9-enoyl chloride (0.374 g, 1.24mmol) was reacted with 2-azidoethanamine (0.107 g, 1.24 mmol) andtriethylamine (0.252 g, 2.49 mmol) in dichloromethane (5 mL) to give

N-(2-azidoethyl)octadec-9-enamide (0.309 g, 71% yield). ¹H NMR (300 MHz,CDCl₃) δ 6.30 (s, 1H), δ 5.29 (m, 2H), δ 3.39 (d, J =2.1 Hz, 2H), δ 3.38(d, J=2.4 Hz, 2H), δ 2.19 (t, J=7.2 Hz, 2H), δ 1.97 (m, 4H), δ 1.59 (t,J=7.5 Hz, 2H), δ 1.26 (m, 20H), δ 9.84 (t, J=6.6 Hz, 3H) ppm; ¹³C NMR(75 MHz, CDCl₃) δ 173.9, 130.2, 129.9, 51.1, 39.1, 36.8, 32.1, 30.0,29.9, 29.7, 29.5, 29.4, 29.3, 27.4, 27.3, 25.9, 22.9, 14.3 ppm; HRMS(ESI) calcd for C₂₀H₃₈N₄O (M+) 350.3046, found 350.3039.

N-(2-azidoethyl)thiophene-2-sulfonamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, thiophene-2-sulfonyl chloride (0.218 g,1.19 mmol) was reacted with 2-azidoethanamine (0.103 g, 1.19 mmol) andtriethylamine (0.241 g, 2.39 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)thiophene-2-sulfonamide (0.221 g, 80% yield). ¹H NMR(300 MHz, CDCl₃) δ 7.62 (d, J=1.2 Hz, 1H), δ 7.59 (d, J=1.2 Hz, 1H),7.08 (t, J=3.9 Hz, 1H), 5.52 (s. 1H), 3.41 (t, J=5.4 Hz, 2H), 3.17 (q,J=5.4, 3.8 Hz, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 140.6, 132.7, 132.6,127.9, 50.9, 42.9 ppm; HRMS (ESI) calcd for C₆H₈N₄O₂S₂ (M+) 232.0089,found 232.0084.

N-(2-azidoethyl)-5-(dimethylamino)naphthalene-1-sulfonamide: As in thesynthesis of N-(2-azidoethyl)tetradecanamide,5-(dimethylamino)naphthalene-1-sulfonyl chloride (0.321 g, 1.19 mmol)was reacted with 2-azidoethanamine (0.103 g, 1.19 mmol) andtriethylamine (0.241 g, 2.38 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-5-(dimethylamino)naphthalene-1-sulfonamide (0.328 g,86% yield). ¹H NMR (300 MHz, CDCl₃) δ 8.52 (d, J=8.4 Hz, 1H), δ 8.28 (d,J=8.4 Hz, 1H), δ 8.22 (d, J=0.9 Hz, 1H), δ 7.53 (t, J=8.1 Hz, 1H), δ7.50 (t, J=7.5 Hz, 1H), δ 7.17 (d, J=7.8 Hz, 1H), δ 5.58 (t, J=1.8 Hz,1H), δ 3.28 (t, J=5.7 Hz, 2H), δ 3.03 (q, J=6.3, 5.7 Hz, 2H), δ 2.85 (s,6H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 152.3, 134.8, 130.9, 130.1, 129.7,128.9, 123.4, 118.9, 115.6, 51.0, 45.6, 42.6 ppm; HRMS (ESI) calcd forC₁₄H₁₇N₅O₂S (M+) 319.1103, found 319.1104.

N-(2-azidoethyl)-2,3,4,5,6-pentamethylbenzenesulfonamide: As in thesynthesis of N-(2-azidoethyl)tetradecanamide,2,3,4,5,6-pentamethylbenzene-1-sulfonyl chloride (0.304 g, 1.23 mmol)was reacted with 2-azidoethanamine (0.106 g, 1.23 mmol) andtriethylamine (0.249 g, 2.46 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-2,3,4,5,6-pentamethylbenzenesulfonamide (0.296 g, 81%yield). ¹H NMR (300 MHz, CDCl₃) δ 5.12 (t, J=3.9 Hz, 1H) δ 3.35 (t,J=5.4 Hz, 2H), δ 3.05 (q, J=6.0, 5.1 Hz, 2H), 2.59 (s, 6H), δ 2.28 (s,3H), 2.24 (s, 6H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 139.9, 136.1, 135.2,134.2, 51.1, 42.3, 19.2, 17.9, 17.3 ppm; HRMS (ESI) calcd forC₁₃H₂₀N₄O₂S (M+) 296.1307, found 296.1304.

N-(2-azidoethyl)benzenesulfonamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, benzenesulfonyl chloride (0.201 g, 1.16mmol) was reacted with 2-azidoethanamine (0.100 g, 1.16 mmol) andtriethylamine (0.235 g, 2.32 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)benzenesulfonamide (0.289 g, 84% yield). ¹H NMR (300MHz, CDCl₃) δ 7.90 (d, J=1.8 Hz, 2H), δ 7.55 (m, 3H), δ 5.47 (s, 1H), δ3.39 (t, J=5.1 Hz, 2H), δ 3.12 (t, J=5.4 Hz, 2H) ppm; ¹³C NMR (75 MHz,CDCl₃) δ 139.8, 133.2, 129.5, 127.2, 50.9, 42.6 ppm; HRMS (ESI) calcdfor C₆H₈N₄O₂S (M+) 226.0524, found 226.0523.

(E)-N-(2-azidoethyl)-4-phenylbut-3-enamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (E)-4-phenylbut-3-enoyl chloride (0.198g, 1.19 mmol) was reacted with 2-azidoethanamine (0.114 g, 1.19 mmol)and triethylamine (0.239 g, 2.37 mmol) in dichloromethane (5 mL) to give(E)-N-(2-azidoethyl)-4-phenylbut-3-enamide (0.168 g, 55% yield). ¹H NMR(300 MHz, CDCl₃) δ 7.68 (d, J=15.6 Hz, 1H), δ 7.45 (d, J=3.3 Hz, 2H), δ7.29 (m, 3H), δ 7.04 (t, J=4.1 Hz, 1H), δ 6.59 (d, J=15.9 Hz, 1H), δ3.55 (q, J=6.0, 5.1 Hz, 2H), δ 3.47 (t, J=1.5 Hz, 2H) ppm; ¹³C NMR (75MHz, CDCl₃) δ 166.9, 141.6, 134.9, 130.1, 129.1, 128.1, 120.8, 51.1,39.4 ppm; HRMS (ESI) calcd for C₁₁H₁₂N₄O (M+) 216.1011, found 216.1005.

N-(2-azidoethyl)-2-(phenylthio)acetamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 2-(phenylthio)acetyl chloride (0.222 g,1.19 mmol) was reacted with 2-azidoethanamine (0.102 g, 1.19 mmol) andtriethylamine (0.240 g, 2.37 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-2-(phenylthio)acetamide (0.179 g, 64% yield).

¹H NMR (300 MHz, CDCl₃) δ 7.29 (m, 4H), δ 7.18 (m, 2H), δ 3.60 (s, 2H),3.34 (m, 4H) ppm;

¹³C NMR (75 MHz, CDCl₃) δ 168.6, 134.8, 129.5, 128.6, 127.1, 50.8, 39.3,37.7 ppm; HRMS (ESI) calcd for C₁₀H₁₂N₄OS (M+) 236.0732, found 236.0729.

N-(2-azidoethyl)palmitamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.338 g. 1.23 mmol) was reacted with2-azidoethanamine (0.106 g, 1.23 mmol) and triethylamine (0.249 g, 2.46mmol) in dichloromethane (5 mL) to give N-(2-azidoethyl)palmitamide(0.336 g, 84% yield). ¹H NMR (300 MHz, CDCl₃) 6 6.11 (s, 1H), δ 3.41 (s,4H), δ 2.17 (t, J=7.5 Hz, 2H), δ 1.60 (m, 2H), δ 1.23 (m, 24H), δ 0.85(t, 6.3 Hz, 3H) ppm;

¹³C NMR (75 MHz, CDCl₃) δ 173.9, 51.1, 39.1, 36.9, 32.1, 29.9, 29.8,29.8, 29.7, 29.6, 29.5, 25.9, 22.9, 14.3 ppm; HRMS (ESI) calcd forC₁₈H₃₆N₄O (M+) 324.2889, found 324.2879.

N-(2-azidoethyl)decanamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, decanoyl chloride (0.251 g, 1.32 mmol)was reacted with 2-azidoethanamine (0.114 g, 1.32 mmol) andtriethylamine (0.267 g, 2.64 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)decanamide (0.262 g, 83% yield). ¹H NMR (300 MHz, CDCI₃)δ 6.49 (s, 1H), δ 3.36 (s, 2H), δ 3.35 (s, 2H), δ 2.14 (t, J=7.2 Hz,2H), δ 1.46 (m, 2H), δ 1.21 (m, 12H), δ 0.81 (t, J=6.0 Hz, 3H) ppm; ¹³CNMR (75 MHz, CDCl₃) δ 174.1, 50.9, 39.1, 36.8, 32.0, 29.7, 29.6, 29.5,29.4, 25.9, 22.8, 14.3 ppm; HRMS (ESI) calcd for C₁₂H₂₄N₄O (M+)240.1950, found 240.1947.

N-(2-azidoethyl)-2-iodobenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 2-iodobenzoyl chloride (0.312 g, 1.17mmol) was reacted with 2-azidoethanamine (0.101 g, 1.17 mmol) andtriethylamine (0.237 g, 2.34 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-2-iodobenzamide (0.272 g, 74% yield). ¹H NMR (300 MHz,CDCl₃) δ 7.84 (d, J=7.2 Hz, 1H), δ 7.33 (m, 2H), δ 7.08 (t, J=3.3 Hz,1H), δ 6.51 (s, 1H), δ 3.54 (s, 2H), δ 3.53 (s, 2H) ppm; ¹³C NMR (75MHz, CDCl₃) δ 169.9, 141.9, 140.0, 131.5, 128.4, 128.4, 92.7, 50.8, 39.6ppm; HRMS (ESI) calcd for C₉H₉IN₄O (M+) 315.9821, found 315.9820.

N-(2-azidoethyl)-4-tert-butylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 4-tert-butylbenzoyl chloride (0.244 g,1.23 mmol) was reacted with 2-azidoethanamine (0.106 g, 1.23 mmol) andtriethylamine (0.249 g, 2.47 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-tert-butylbenzamide (0.221 g, 73% yield).

¹H NMR (300 MHz, CDCl₃) δ 7.73 (d, J=6.6 Hz, 2H), δ 7.43 (d, J=9.0 Hz,2H), δ 6.95 (t, J=3.9 Hz, 1H), δ 3.59 (q, J=5.4, 5.7 Hz, 2H), δ 3.50 (t,J=5.1 Hz, 2H), δ 1.31 (s, 9H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.2,155.4, 131.4, 127.2, 125.8, 51.1, 39.7, 35.2, 31.4 ppm; HRMS (ESI) calcdfor C₁₃H₁₈N₄O (M+) 246.1480, found 246.1479.

N-(2-azidoethyl)-3,5-difluorobenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 3,5-difluorobenzoyl chloride (0.219 g,1.24 mmol) was reacted with 2-azidoethanamine (0.107 g, 1.24 mmol) andtriethylamine (0.251 g, 2.48 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-3,5-difluorobenzamide (0.280 g, 59% yield).

¹H NMR (300 MHz, CDCl₃) δ 7.32 (s, 2H), 7.29 (s, 1H), 6.91 (t, J=2.4 Hz,1H), 3.58 (q, J=5.7, 5.1 Hz, 2H), 3.51 (t, J=4.8 Hz, 2H) ppm; ¹³C NMR(75 MHz, CDCl₃) δ 165.9, 164.7, 161.5, 161.4, 137.6, 110.7, 106.9, 50.7,39.9 ppm; HRMS (ESI) calcd for C₉H₈F2N₄O₂S (M+) 226.0666, found226.0662.

N-(2-azidoethyl)-2,4,6-trichlorobenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.301 g, 1.23 mmol) was reacted with2-azidoethanamine (0.106 g, 1.23 mmol) and triethylamine (0.249 g, 2.47mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-2,4,6-trichlorobenzamide (0.317 g, 88% yield). ¹H NMR(300 MHz, CDCl₃) δ 7.27 (2H, s), δ 6.88 (s, 1H), δ 3.54 (s, 2H), δ 3.53(s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 164.4, 135.9, 134.3, 132.9,128.2, 50.7, 39.4 ppm; HRMS (ESI) calcd for C₉H₇N₄O (M+) 291.9685, found291.9681.

N-(2-azidoethyl)-2-naphthamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 2-naphthoyl chloride (0.237 g, 1.24mmol) was reacted with 2-azidoethanamine (0.107 g, 1.24 mmol) andtriethylamine (0.252 g, 2.49 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-2-naphthamide (0.234 g, 77% yield). ¹H NMR (300 MHz,CDCl₃) δ 8.69 (s, 1H), δ 7.84 (m, 4H), δ 7.50 (m, 2H), 6.97 (t, J=4.2Hz, 1H), δ 3.68 (q, J=4.8, 1.2 Hz, 2H), 3.56 (t, J=3.0 Hz, 2H) ppm; ¹³CNMR (75 MHz, CDCl₃) δ 168.3, 135.1, 132.8, 131.5, 129.2, 128.8, 128.0,127.9, 127.1, 123.8, 51.2, 39.8 ppm; HRMS (ESI) calcd for C₁₃H₁₂N₄O (M+)240.1011, found 240.1007.

N-(2-azidoethyl)-4-heptylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 4-heptylbenzoyl chloride (0.289 g, 1.21mmol) was reacted with 2-azidoethanamine (0.104 g, 1.21 mmol) andtriethylamine (0.245 g, 2.42 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-heptylbenzamide (0.260 g, 75% yield). ¹H NMR (300MHz, CDCl₃) δ 7.73 (d, J=7.8 Hz, 2H), δ 7.19 (d, J=7.8 Hz, 3H), δ 3.57(q, J=5.7, 5.4 Hz, 2H), δ 3.47 (t, J=5.7 Hz, 2H), δ 2.61 (t, J=7.5 Hz,2H), δ 1.61 (m, 2H), δ 1.26 (m, 8H), δ 0.87 (t, J=6.0 Hz, 3H) ppm; ¹³CNMR (75 MHz, CDCl₃) δ 168.3, 147.3, 131.7, 128.8, 127.4, 50.9, 39.7,36.1, 32.0, 31.4, 29.4, 29.3, 22.9, 14.3 ppm; HRMS (ESI) calcd forC₁₆H₂₄N₄O (M+) 288.1950, found 288.1943.

N-(2-azidoethyl)-4-butylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.242 g, 1.22 mmol) was reacted with2-azidoethanamine (0.105 g, 1.22 mmol) and triethylamine (0.246 g, 2.43mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-butylbenzamide (0.224 g, 75% yield). ¹H NMR (300 MHz,CDCl₃) δ 7.73 (d, J=8.4 Hz, 2H), δ 7.39 (t, J=1.8 Hz, 1H), δ 7.17 (d,J=8,1 Hz, 2H), δ 3.55 (q, J=8.7, 5.7 Hz, 2H), δ 3.45 (t, J=5.7 Hz, 2H),δ 2.60 (t, J=7.8 Hz, 2H), δ 1.56 (m, 2H), δ 1.30 (m, 2H), δ 0.90 (t,J=4.2 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.5, 147.2, 131.7, 128.8,127.4, 50.9, 39.7, 35.7, 33.5, 22.5, 14.1 ppm; HRMS (ESI) calcd forC₁₃H₁₈N₄O (M+) 246.1481, found 246.1476.

N-(2-azidoethyl)-4-hexylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 4-hexylbenzoyl chloride (0.293 g, 1.30mmol) was reacted with 2-azidoethanamine (0.112 g, 1.30 mmol) andtriethylamine (0.264 g, 2.61 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-hexylbenzamide (0.299 g, 84% yield). ¹H NMR (300 MHz,CDCl₃) δ 7.75 (d, J=8.1 Hz, 2H), δ 7.43 (t, J−3.9 Hz, 1H), δ 7.17 (d,J=7.8 Hz, 2H), 6 3.55 (q, J=6.3, 5.7 Hz, 2H), 6 3.46 (t, J=5.7 Hz, 2H),δ 2.59 (t, J=7.5 Hz, 2H), δ 1.58 (m, 2H), δ 1.29 (m, 4H), δ 0.87 (t,J=6.9 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.6, 147.3, 131.7, 130.3,128.8, 127.5, 50.9, 39.7, 35.9, 31.6, 31.1, 22.7, 14.2 ppm; HRMS (ESI)calcd for C₁₅H₂₂N₄O (M+) 274.1794, found 274.1789.

N-(2-azidoethyl)-4-pentylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, 4-pentylbenzoyl chloride (0.283 g, 1.35mmol) was reacted with 2-azidoethanamine (0.116 g, 1.35 mmol) andtriethylamine (0.273 g, 2.69 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-pentylbenzamide (0.267 g, 76% yield). ¹H NMR (300MHz, CDCl₃) δ 7.74 (d, J=8.1 Hz, 2H), δ 7.61 (t, J=5.1 Hz, 1H), δ 7.15(d, J=8.4 Hz, 2H), δ 3.54 (q, J=5.7, 5.1 Hz, 2H), δ 3.44 (t, J=5.7 Hz,2H), δ 2.58 (t, J=7.5 Hz, 2H), δ 1.57 (m, 2H), δ 1.26 (m, 4H), δ 0.86(t, J=6.6 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.6, 147.2, 131.7,128.7, 127.5, 50.8, 39.7, 35.9, 31.6, 31.1, 22.7, 14.2 ppm; HRMS (ESI)calcd for C₁₄H₂₀N₄O (M+) 260.1637, found 260.1632.

N-(2-azidoethyl)biphenyl-4-carboxamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.283 g, 1.31 mmol) was reacted with2-azidoethanamine (0.113 g, 1.31 mmol) and triethylamine (0.264 g, 2.61mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)biphenyl-4-carboxamide (0.297 g, 85% yield). ¹H NMR (300MHz, CDCl₃) δ 7.88 (d, 2H), δ 7.67 (m, 4H), δ 7.44 (m, 3H), δ 6.63 (s,1H), δ 3.67 (q, J=6.0, 1.8 Hz, 2H), δ 3.58 (t, J=6.0 Hz, 2H) ppm; ¹³CNMR (75 MHz, CDCl₃) δ 167.8, 144.8, 140.1, 132.9, 129.2, 128.3, 127.8,127.5, 127.4, 51.2, 39.7 ppm; HRMS (ESI) calcd for C₁₅H₁₄N₄O (M+)266.1168, found 266.1162.

N-(2-azidoethyl)-4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamide: As inthe synthesis of N-(2-azidoethyl)tetradecanamide, (0.529 g, 1.38 mmol)was reacted with 2-azidoethanamine (0.119 g, 1.38 mmol) andtriethylamine (0.279 g, 2.75 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamide (0.331 g,69% yield). ¹H NMR (300 MHz, CD₃OD) δ 6.84 (s, 1H), δ 3.91 (s, 3H), δ3.50 (t, J=3.6 Hz, 2H), δ 3.25 (t, J=1.5 Hz, 2H) ppm; ¹³C NMR (75 MHz,CD₃OD) δ 161.7, 127.7, 114.7, 111.4, 97.8, 50.4, 38.9, 35.1 ppm; HRMS(ESI) calcd for C₈H₉N₅O (M+) 348.9174, found 348.9183.

N-(2-azidoethyl)-1H-pyrrole-2-carboxamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.249 g, 1.17 mmol) was reacted with2-azidoethanamine (0.101 g, 1.17 mmol) and triethylamine (0.237 g, 2.34mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-1H-pyrrole-2-carboxamide (0.137 g, 66% yield). ¹H NMR(300 MHz, CD₃OD) δ 6.88 (d, J=1.5 Hz, 1H), δ 6.77 (d, J=2.4 Hz, 1H), δ6.14 (t, J=2.4 Hz, 1H), δ 3.46 (t, J=5.7 Hz, 2H), δ 3.37 (q, J=5.7, 14.7Hz, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ 162.9, 125.6, 122.2, 121.9,110.9, 109.2, 50.6, 38.9 ppm; HRMS (ESI) calcd for C₇H₉N₅O (M+)179.0807, found 179.0803.

N-(2-azidoethyl)-4-bromo-1H-pyrrole-2-carboxamide: As in the synthesisof N-(2-azidoethyl)tetradecanamide, (0.408 g, 1.34 mmol) was reactedwith 2-azidoethanamine (0.115 g, 1.34 mmol) and triethylamine (0.270 g,2.67 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-bromo-1H-pyrrole-2-carboxamide (0.299 g, 82% yield).¹H NMR (300 MHz, CD₃OD) δ 6.93 (s, 1H), δ 6.80 (s, 1H), δ 3.49 (t, J=0.6Hz, 2H), δ 3.41 (t, J=0.9 Hz, 2H) ppm;

¹³C NMR (75 MHz, CD₃OD) δ 161.7, 126.1, 122.0, 112.4, 96.4, 50.5, 38.9ppm; HRMS (ESI) calcd for C₇H₈BrN₅O (M+) 256.9912, found 256.9908.

N-(2-azidoethyl)-4-nonylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, the acid chloride (0.354 g, 1.40 mmol)was reacted with 2-azidoethanamine (0.121 g, 1.40 mmol) andtriethylamine (0.284 g, 2.80 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-nonylbenzamide (0.339 g, 80% yield). ¹H NMR (300 MHz,CDCl₃) δ 6.21 (s, 1H), δ 3.40 (s, 4H), δ 2.19 (t, J=7.2 Hz, 2H), δ 1.62(t, J=6.0 Hz, 2H), δ 1.22 (bs, 14 H), δ 0.842 (t, J=6.3 Hz, 3H) ppm; ¹³CNMR (75 MHz, CDCl₃) δ 173.8, 51.1, 30.1, 36.8, 32.1, 29.8, 29.7, 29.6,29.5, 29.2, 25.9, 22.9, 14.3 ppm; HRMS (ESI) calcd for C₁₄H₂₈N₄O (M+)268.2263, found 268.2259.

N-(2-azidoethyl)-4-nonylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.383 g, 1.43 mmol) the acid chloridewas reacted with 2-azidoethanamine (0.124 g, 1.43 mmol) andtriethylamine (0.290 g, 2.87 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-nonylbenzamide (0.441 g, 97% yield). ¹H NMR (300 MHz,CDCl₃) δ 7.72 (d, 2H), δ 7.26 (t, 1H), δ 7.18 (d, 2H), δ 3.57 (q, 2H), δ3.45 (t, 2H), δ 2.60 (t, 2H), δ 1.58 (m, 2H), δ 1.27 (m, 12H), δ 0.86(t, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.5, 147.3, 131.7, 128.8,127.4, 50.9, 39.7, 36.1, 32.1, 31.5, 29.8, 29.7, 29.6, 29.5, 22.9, 14.4ppm; HRMS (ESI) calcd for C₁₈H₂₈N₄O (M+) 316.2263, found 316.2268.

N-(2-azidoethyl)-4-octylbenzamide: As in the synthesis ofN-(2-azidoethyl)tetradecanamide, (0.262 g, 1.19 mmol) the acid chloridewas reacted with 2-azidoethanamine (0.103 g, 1.19 mmol) andtriethylamine (0.242 g, 2.39 mmol) in dichloromethane (5 mL) to giveN-(2-azidoethyl)-4-octylbenzamide (0.220 g, 69% yield). ¹H NMR (300 MHz,CDCl₃) δ 7.73 (d, 2H), δ 7.37 (t, 1H), δ 7.17 (d, 2H), δ3.56 (q, 2H), δ3.44 (t, 2H), δ 2.59 (t, 2H), δ 1.58 (m, 2H), δ 1.27 (m, 10H), δ0.86 (t,3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.4, 147.3, 131.7, 128.8, 127.4,50.9, 39.7, 36.1, 32.1, 31.5, 29.7, 29.5, 29.5, 22.9, 14.3 ppm; HRMS(ESI) calcd for C₁₇H₂₈N₄O (M+) 302.2107, found 302.2104.

(E)-N-(2-azidoethyl)-2-methyl-3-phenylacrylamide: To a 25 mLround-bottomed flask equipped with a magnetic stir bar was added(E)-2-methyl-3-phenylacrylic acid (0.0.512 g, 3.15 mmol) anddichloromethane (10 mL). Oxalyl chloride (0.400 g, 3.15 mmol) was addeddropwise to the reaction mixture and allowed to stir for one hour. Then,the reaction mixture was concentrated de vacuo. To the crude mixture wasthen added dichloromethane (10 mL), 2-azidoethanamine (0.299 g, 3.47mmol) and then triethylamine (0.351 g, 3.47 mmol) and allowed to stirfor two hours. The reaction mixture was then concentrated de vacuo andthen purified via silica gel column chromatography (100% dichloromethaneto 1:40 methanol:dichloromethane) to give(E)-N-(2-azidoethyl)-2-methyl-3-phenylacrylamide (0.698 g, 96% yield).¹H NMR (300 MHz, CDCl₃) δ 7.39 (m, 6H), δ 7.01 (s, 1H), δ 3.51 (t, J=4.5Hz, 2H), δ 3.45 (t, J=4.8 Hz, 2H), δ 2.13 (s, 3H) ppm; ¹³C NMR (75 MHz,CDCl₃) δ 170.5, 136.2, 134.5, 132.0, 130.3, 129.6, 128.9, 128.6, 128.3,50.9, 39.8, 14.5 ppm; HRMS (ESI) calcd for C₁₂H₁₄N₄O (M+) 230.1168,found 230.1165.

N-(2-azidoethyl)-2′,4′-difluoro-3-hydroxybiphenyl-4-carboxamide: To a 25mL round-bottomed flask equipped with a magnetic stir bar was added2′,4′-difluoro-3-hydroxybiphenyl-4-carboxylic acid (0.301, 1.20 mmol),N,N-Dimethylformamide (5 mL), N,N′-Dicyclohexylcarbodiimide (0.248 g,1.20 mmol) and n-methylmorpholine (0.25 mL). The reaction mixture wascooled to 0° C. and allowed to stir. Then, 2-azidoethanamine (0.1037 g,1.20 mmol) was added dropwise and allowed to slowly warm to roomtemperature while stirring for 24 hr. The reaction mixture was dilutedwith water, extracted with dichloromethane, washed with 1N HCl, washedwith saturated sodium bicarbonate, washed with brine and thenconcentrated de vacuo. The resulting residue was then purified viasilica gel column chromatography (1:40 methanol: dichloromethane to 1:10methanol:dichloromethane) to giveN-(2-azidoethyl)-2′,4′-difluoro-3-hydroxybiphenyl-4-carboxamide (0.232g, 61% yield). ¹H NMR (300 MHz, CDCl₃) δ 7.60 (s, 1H), δ 7.47 (d, J=6.0Hz, 1H), δ 7.29 (m, 2H), δ 7.02 (d, J=6.6 Hz, 1H), δ 6.88 (m, 2H) ppm;¹³C NMR (75 MHz, CDCl₃) δ 170.3, 160.8, 135.1, 131.3, 131.2, 131.3,131.2, 126.8, 118.8, 114.6, 112.0, 111.8, 104.8, 104.6, 104.3, 50.7,39.3 ppm; HRMS (ESI) calcd for C₁₅H₁₂F₂N₄O₃ (M+) 318.0928, found318.0933.

General procedure for click reactions and subsequent Boc deprotection:The terminal alkyne (1.0 equiv.) was dissolved in a 1:1:1 mixture ofethanol, water and methylene chloride (ca. 9 mL per 0.300 g of terminalalkyne). To this solution, the appropriate azide (1.0 equiv.) was addedwhile stirring vigorously at room temperature. Copper (II) sulfate (15mol %) and sodium ascorbate (45 mol %) were then added sequentially tothe solution. Reaction mixtures were allowed to stir until completionvia TLC analysis (12-24 hrs). The solvents were then removed de vacuo inwhich the resulting residue was dissolved in dichloromethane andpurified via silica gel column chromatography (1:40methanol:dichloromethane to 1:10 methanol: dichloromethane). To removethe Boc protecting group, the resulting product was then dissolved in a1:4 trifluoroacetic acid: dichloromethane mixture and allowed to stirfor 5 hr. Upon completion, the reaction mixture was concentrated devacuo and then left on a high vacuum overnight. Then, methanolsupplemented with HCl was added to the product forming the HCl salt ofthe deprotected product and then was concentrated de vacuo. Theresulting residue was washed with diethyl ether and then placed on ahigh vacuum overnight.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-(phenylthio)acetamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.112 g, 0.405 mmol)was reacted with N-(2-azidoethyl)-2-(phenylthio)acetamide (0.096 g,0.405 mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(2-(phenylthio)acetamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.45 (s, 1H), δ 7.19 (m, 5H), δ 7.13 (s, 1H),δ 6.43 (s, 1H), δ 6.13 (bs, 2H), δ 4.29 (s, 2H), δ 3.68 (s, 2H), δ 3.57(s, 2H), δ 2.56 (s, 2H), δ 2.35 (s, 2H), δ 1.52 (m, 15H) ppm; ¹³C NMR(75 MHz, CDCl₃) δ 187.8, 172.0, 169.1, 162.4, 156.9, 135.0, 129.5,128.3, 126.8, 121.8, 85.00, 49.4, 39.9, 37.4, 29.4, 28.9, 28.4, 28.2,27.6, 25.6 ppm; HRMS (ESI) calcd for C₂₅H₃₅N₇O₃S (M+) 513.2522, found513.2522, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-(phenylthio)acetamidehydrochloride (0.133 g, 73% yield). ¹H NMR (300 MHz, CD_(:3)0D) δ 8.47(s, 1H), δ 7.30 (s, 4H), δ 7.19 (s, 1H), δ 6.58 (s, 1H), δ 4.66 (s, 2H),δ 3.76 (s, 2H), δ 3.64 (s, 2H), δ 2.84 (s, 2H), δ 2.34 (s, 2H), δ 1.73(s, 2H), δ 1.64 (s, 2H), δ 1.26 (s, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ170.9, 159.3, 158.9, 147.2, 135.6, 128.1, 128.9, 127.6, 126.6, 108.7,108.6, 39.1, 37.5, 37.2, 36.6, 36.1, 30.8, 28.1, 27.9, 27.7, 24.2, 23.7,23.6 ppm; HRMS (ESI) calcd for C₂₀H₂₇N₇OS (M+) 413.1998, found 413.1991.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)thiophene-2-sulfonamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.105 g, 0.379 mmol)was reacted with N-(2-azidoethyl)thiophene-2-sulfonamide (0.099 g, 0.379mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(thiophene-2-sulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.49 (s, 3H), δ 7.39 (s, 1H), δ 6.99 (s, 1H),δ 6.41 (bm, 3H), δ 443 (s, 2H), δ 3.42 (s, 2H), δ 2.54 (s, 2H), δ 2.09(s, 2H), δ 1.51 (m, 13H), δ 1.19 (s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ150.8, 149.4, 148.1, 141.1, 138.3, 132.2, 132.1, 127.7, 122.6, 85.2,53.8, 50.2, 43.2, 31.2, 29.9, 29.2, 28.8, 28.1, 25.5 ppm; HRMS (ESI)calcd for C₂₁H₃₁N₇O₄S₂ (M+) 509.1879, found 509.1879, which wassubsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)thiophene-2-sulfonamidehydrochloride (0.098 g, 58% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.37 (s,1H), δ 7.76 (s, 1H), δ 7.57 (s, 1H), δ 7.11 (s, 1H), δ 6.46 (s, 1H), δ4.79 (s, 2H), δ 3.55 (s, 2H), δ 2.50 (s, 2H), δ 1.66-1.18 (bm, 8H) ppm;¹³C NMR (100 MHz, CD₃OD) δ 175.6, 155.6, 147.2, 140.9, 132.7, 132.3,127.8, 127.7, 108.8, 53.1, 42.2, 36.8, 28.1, 27.8, 27.5, 24.9, 24.3,23.8 ppm; HRMS (ESI) calcd for C₁₆H₂₃N₇O₂S₂ (M+) 409.1355, found409.1354.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-5-(dimethylamino)naphthalene-1-sulfonamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.112 g, 0.403 mmol)was reacted withN-(2-azidoethyl)-5-(dimethylamino)naphthalene-1-sulfonamide (0.140 g,0.403 mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(5-(dimethylamino)naphthalene-1-sulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 8.48 (d, J=8.4 Hz, 1H), δ 8.24 (d, J=8.4 Hz,1H), δ 8.17 (d, J=7.2 Hz, 1H), δ 7.44 (m, 3H), δ 7.09 (s, 1H), δ 7.07(d, J=7.5 Hz, 1H), δ 6.44 (s, 1H), δ 6.09 (bs, 2H), δ 4.32 (s, 2H), δ3.36 (s, 2H), δ 2.52 (s, 2H), δ 2.22 (s, 2H), δ 1.43 (m, 13H), δ 1.22(s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 176.9, 152.1, 149.6, 148.0,138.6, 135.1, 130.7, 130.1, 129.7, 129.4, 128.5, 123.3, 122.4, 119.1,115.5, 84.9, 67.5, 50.3, 50.2, 45.6, 42.9, 37.9, 29.1, 28.9, 28.2, 28.0,25.5 ppm; HRMS (ESI) calcd for C₂₉H₄₀N₈O₄S (M+) 596.2893, found596.2881, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-5-(dimethylamino)naphthalene-1-sulfonamidehydrochloride (0.139 g, 65% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.70 (t,J=4.8 Hz, 2H), δ 8.31 (s, 1H), δ 8.08 (s, 2H), δ 7.82 (s, 2H), δ 6.43(s, 1H), δ 4.55 (s, 2H), δ 3.32 (s, 8H), 2.63 (s, 2H), δ 2.48 (s, 2H), δ1.66 (s, 4H), δ 1.40 (s, 2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 159.9,147.3, 140.7, 136.8, 129.9, 129.3, 127.8, 127.7, 126.5, 119.3, 108.6,108.4, 76.7, 67.3, 51.5, 42.3, 37.4, 36.5, 28.3, 27.9, 27.6, 24.1, 24.0,23.7 ppm; HRMS (ESI) calcd for C₂₄H₃₂N₈O₂S (M+) 496.2369, found496.2359.

tert-butyl2-amino-4-(5-(1-(2-(phenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylatehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.114 g, 0.410 mmol)was reacted with N-(2-azidoethyl)benzenesulfonamide (0.104 g, 0.410mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(phenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylateNMR (300 MHz, CDCl₃) δ 7.81 (d, J=6.9 Hz, 2H), δ 7.44 (m, 5H), δ 6.44(s, 1H), δ 6.07 (s, 2H), δ 4.42 (t, J=5.7 Hz, 2H), δ 3.36 (t, J=5.4 Hz,2H), δ 2.57 (t, J=7.2 Hz, 2H), δ 2.20 (s, 2H), δ 1.47 (m, 13H), δ 1.29(s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 202.9, 149.5, 148.2, 140.2,132.8, 129.4, 127.1, 122.5, 106.5, 85.0, 53.7, 50.3, 42.9, 32.7, 31.2,29.9, 29.2, 28.9, 28.2, 26.3, 25.5 ppm; HRMS (ESI) calcd for C₂₃H₃₃N₇O₄S(M+) 503.2315, found 503.2310, which was subsequently deprotected togive tert-butyl2-amino-4-(5-(1-(2-(phenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylatehydrochloride (0.142 g, 64% yield). ¹H NMR (300 MHz, CD₃OD) δ 7.81 (d,J=6.6 Hz, 2H), δ 7.56 (m, 4H), δ 6.47 (s, 1H), δ 4.62 (s, 2H), δ 3.41(s, 2H), δ 2.78 (s, 2H), δ 2.48 (s, 2H), δ 1.72 (s, 2H), δ 1.63 (s, 2H),δ 1.42 (s, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ 176.2, 165.6, 259.9,147.3, 140.2, 132.8, 129.3, 127.7, 126.8, 108.5, 108.4, 515.8, 42.3,28.1, 27.9, 27.6, 24.1 ppm; HRMS (ESI) calcd for C₁₈H₂₅N₇O₂S (M+)403.1790, found 403.1781.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2,3,4,5,6-pentamethylbenzenesulfonamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.120 g, 0.434 mmol)was reacted withN-(2-azidoethyl)-2,3,4,5,6-pentamethylbenzenesulfonamide (0.141 g, 0.434mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(2,3,4,5,6-pentamethylphenylsulfonamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.30 (s, 1H), δ 7.01 (s, 1H), δ 6.44 (s, 1H),δ 6.17 (s, 2H), δ 4.35 (s, 2H), δ 3.34 (s, 2H), δ2.47 (s, 2H), δ 2.48(s, 6H), δ 2.20 (m, 11H), δ 1.43 (m, 15H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ149.6, 148.1, 139.7, 136.2, 134.9, 134.3, 122.4, 84.9, 53.7, 50.2, 42.5,31.1, 29.3, 28.9, 28.4, 28.2, 25.6, 19.1, 17.9, 17.2 ppm; HRMS (ESI)calcd for C₂₈H₄₃N₇O₄S (M+) 573.3097, found 573.3086, which wassubsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2,3,4,5,6-pentamethylbenzenesulfonamidehydrochloride (0.143 g, 76% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.11 (s,1H), δ 6.42 (s, 1H), δ 4.48 (s, 2H), δ 3.34 (s, 2H), δ 2.65 (s, 2H), δ2.40 (s, 8H), δ 2.12 (s, 9H), δ 1.58 (s, 4H), δ 1.19 (s, 2H) ppm; ¹³CNMR (100 MHz, CD₃OD) δ 159.9, 147.3, 139.6, 136.1, 134.8, 134.0, 127.8,127.6, 108.6, 108.4, 54.1, 51.5, 41.8, 36.5, 28.2, 28.1, 27.7, 24.1,23.7, 18.2, 16.8, 16.1 ppm; HRMS (ESI) calcd for C₂₃H₃₅N₇O₂S (M+)473.2573, found 473.2565.

(E)-N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-methyl-3-phenylacrylamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.1103 g, 0.397mmol) was reacted with (E)-N-(2-azidoethyl)-2-methyl-3-phenylacrylamide(0.092 g, 0.397 mmol) following the general click procedure to give(E)-tert-butyl2-amino-4-(5-(1-(2-(2-methyl-3-phenylacrylamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.28 (m, 7H), δ 6.94 (s, 2H), 6.06 (s, 2H), δ4.46 (s, 2H), δ 3.79 (s, 2H), δ 2.61 (s, 2H), δ 2.27 (s, 2H), δ 1.99 (s,3H), δ 1.49 (bs, 11H), δ 1.18 (s, 4H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ192.4, 191.3, 170.4, 150.9, 140.2, 136.2, 134.8, 131.6, 129.6, 128.6,128.1, 122.1, 95.8, 85.2, 74.3, 53.7, 52.6, 50.7, 49.4, 40.1, 29.9,29.3, 28.9, 28.2, 25.6, 14.4 ppm; HRMS (ESI) calcd for C₂₇H₃₇N₇O₃ (M+)507.2958, found 507.2942, which was subsequently deprotected to give(E)-N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-methyl-3-phenylacrylamidehydrochloride (0.148 g, 84% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.78 (s,1H), δ 7.33 (s, 4H), δ 7.26 (s, 1H), δ 7.19 (s, 1H), δ 6.42 (s, 1H), δ4.78 (s, 2H), δ 3.84 (s, 2H), δ 2.87 (s, 2H), δ 2.44 (s, 2H), δ 1.99 (s,3H), δ 1.76 (s, 2H), δ 1.59 (s, 2H), δ 1.42 (s, 2H) ppm; ¹³C NMR (100MHz, CD₃OD) δ 174.7, 136.0, 134.4, 131.5, 129.3, 128.7, 128.3, 128.0,127.6, 108.6, 94.6, 53.1, 39.2, 27.6, 27.9, 27.7, 27.6, 24.1, 23.8,23.1, 14.3, 13.4 ppm; HRMS (ESI) calcd for C₂₂H₂₉N₇O (M+) 407.2434,found 407.2429.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)cinnamamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.106 g, 0.384 mmol)was reacted with N-(2-azidoethyl)cinnamamide (0.083 g, 0.384 mmol)following the general click procedure to give (E)-tert-butyl2-amino-4-(5-(1-(2-cinnamamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.67 (s, 1H), δ 7.51 (d, J=11.1 Hz, 1H), δ7.28 (m, 6H), δ 6.45 (t, J=14.1 Hz, 2H), δ 6.08 (s, 2H), δ 4.47 (s, 2H),δ 3.79 (s, 2H), δ 2.57 (s, 2H), δ 2.23 (s, 2H), δ 1.50 (bs, 13H), δ 1.28(s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 166.9, 150.4, 149.5, 148.3,141.2, 138.9, 134.9, 129.9, 128.9, 128.0, 122.1, 120.8, 106.5, 84.8,53.7, 49.5, 39.9, 31.1, 29.3, 28.9, 28.3, 28.2, 25.6 ppm; HRMS (ESI)calcd for C₂₆H₃₅N₇O₃ (M+) 493.2801, found 493.2800, which wassubsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)cinnamamidehydrochloride (0.097 g, 59% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.10 (s,1H), δ 7.49 (s, 3H), δ 7.32 (s, 3H), δ 6.30 d, J=10.8 Hz, 1H), δ 6.39(s, 1H), δ 4.66 (s, 2H), δ 3.83 (s, 2H), δ 2.73 (s, 2H), δ 2.40 (s, 2H),δ 1.57 (s, 2H), δ 1.55 (s, 2H), δ 1.36 (s, 2H) ppm; ¹³C NMR (100 MHz,CD₃OD) δ 167.8, 160.5, 150.2, 147.3, 141.1, 134.8, 130.7, 129.9, 128.8,127.8, 127.6, 124.9, 23 9, 120.2, 108.5, 108.3, 53.1, 39.3, 36.5, 30.6,28.4, 28.1, 27.6, 26.5, 24.2, 24.1, 23.7 ppm; HRMS (ESI) calcd forC₂₁H₂₇N₇O (M+) 393.2277, found 393.2273.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)heptadec-8-enamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (g, mmol) was reactedwith N-(2-azidoethyl)octadec-9-enamide (g, mmol) following the generalclick procedure to give tert-butyl2-amino-4-(5-(1-(2-heptadec-8-enamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.26 (s, 1H), δ 6.81 (s, 1H), δ 6.42 (s, 2H),δ 5.88 (s, 1H), δ 5.27 (s, 2H), δ 4.38 (s, 2H), δ 3.65 (s, 2H), δ 2.60(s, 2H), δ 2.09 (s, 2H), δ 1.53-1.01 (m, 35H), 0.79 (t, J=6.3 Hz, 3H)ppm; ¹³C NMR (75 MHz, CDCl₃) δ 174.2, 173.8, 148.3, 130.3, 130.1, 129.9,129.8, 121.9, 85.1, 67.1, 49.5, 39.5, 39.1, 38.0, 37.7, 36.7, 36.6,32.8, 32.3, 32.1, 31.7, 29.9, 29.8, 29.7, 29.5, 29.3, 29.2, 28.9, 28.7,28.1, 28.0, 27.9, 27.4, 27.3, 27.3, 26.9, 25.9, 25.6, 25.3, 22.9, 22.8,22.6, 14.3, 14.2 ppm; HRMS (ESI) calcd for C₃₅H₆₁N₇O₃ (M+) 627.4836,found 627.4823, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)ethyl)-1H-1,2,3-triazol-1-yl)pentyl)heptadec-8-enamidehydrochloride (0.128 g, 66% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.36 (s,1H), δ 6.96 (s, 1H), δ 6.45 (s, 1H), δ 6.09 (s, 1H), δ 4.58 (s, 2H), δ3.58 (s, 2H), δ 2.75 (s, 2H), δ 2.10 (s, 2H), δ 1.96 (s, 4H), δ 1.69 (s,2H), δ 1.41 (m, 4H), 1.23 (s, 24H), δ 0.84 (s, 3H) ppm; ¹³C NMR (100MHz, CD₃OD) δ 175.5, 158.8, 155.7, 147.3, 129.7, 129.6, 127.6, 108.5,94.6, 76.7, 51.3, 50.4, 48.6, 48.4, 48.2, 47.9, 47.8, 47.5, 47.3, 38.9,37.5, 36.6, 45.9, 45.8, 33.9, 32.6, 31.9, 31.5, 29.8, 29.5, 29.4, 29.3,29.2, 29.1, 28.2, 27.8, 27.0, 25.8, 24.9, 24.2, 23.8, 22.5, 13.5, 13.3ppm; HRMS (ESI) calcd for C₃₀H₅₃N₇O (M+) 527.4312, found 527.4298.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)decanamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.114 g, 0.412 mmol)was reacted with N-(2-azidoethyl)decanamide (0.099 g, 0.412 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-decanamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (400 MHz, CDCl₃) δ 7.23 (s, 1H), δ 6.57 (s, 1H), δ 6.43 (s, 1H),δ 6.09 (s, 2H), δ 4.38 (s, 2H), δ 3.67 (s, 2H), δ 2.61 (t, J=5.4 Hz,2H), δ 2.08 (s, 2H), δ 2.08 (t, J=5.7 Hz, 2H), δ 1.42 (m, 15H), δ 1.17(m, 14H), δ 0.79 (t, J=4.5 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ174.2, 149.7, 148.4, 138.8, 121.9, 106.6, 84.9, 49.5, 39.5, 36.7, 32.1,31.3, 30.6, 29.9, 29.7, 29.6, 29.5, 29.5, 29.3, 29.0, 28.3, 28.2, 25.9,25.6, 25.5, 22.9, 14.3 ppm; HRMS (ESI) calcd for C₂₇H₄₇N₇O₃ (M+)517.3740, found 517.3736, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)decanamidehydrochloride (0.137 g, 73% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.55 (s,1H), δ 6.53 (s, 1H), 4.72 (s, 2H), δ 3.75 (s, 2H), 2.89 (s, 2H), δ 2.54(t, J=6.8 Hz, 2H), δ 2.16 (t, J=7.2 Hz, 2H), δ 1.81 (s, 2H), δ 1.69 (s,2H), δ 1.49 (m, 4H), δ 1.28 (s, 12H), δ 0.89 (t, 3H) ppm; ¹³C NMR (75MHz, CD₃OD) δ 175.7, 147.3, 128.5, 127.6, 125.1, 120.8, 108.6, 108.4,105.6, 63.1, 59.3, 52.5, 48.6, 48.3, 48.1, 47.9, 47.7, 47.5, 57.3, 38.7,336.6, 35.8, 36.6, 35.8, 31.8, 30.6, 29.4, 29.3, 29.3, 29.2, 28.0, 27.8,27.7, 25.8, 24.1, 23.9, 23.3, 22.6 ppm; HRMS (ESI) calcd for C₂₂H₃₉N₇O(M+) 417.3216, found 417.3209.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)dodecanamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.107 g, 0.387 mmol)was reacted with N-(2-azidoethyl)dodecanamide (0.104 g, 0.387 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-dodecanamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.36 (s, 1H), δ 6.94 (s, 1H), δ 6.49 (s, 1H),δ 6.23 (s, 2H), δ 4.46 (t, J=5.1 Hz, 2H), δ 3.74 (q, J=5.1, 5.7 Hz, 2H),δ 2.68 (t, J=7.5 Hz, 2H), δ 2.34 (t, J=6.9 Hz, 2H), δ 2.16 (t, J=7.5 Hz,2H), δ 1.54 (m, 13H), δ 1.47 (m, 2H), δ 1.24 (m, 18H), δ 0.87 (t, J=6.6Hz, 3H), ppm; ¹³C NMR (75 MHz, CDCl₃) δ 174.3, 150.4, 149.5, 148.3,138.5, 121.9, 106.5, 84.9, 49.5, 39.5, 36.6, 34.1, 32.1, 29.8, 29.8,29.7, 29.6, 29.5, 29.3, 28.9, 28.2, 28.1, 29.0, 26.9. 25.6, 22.9, 14.3ppm; HRMS (ESI) calcd for C₂₉H₅₁N₇O₃ (M+) 545.4053, found 545.4053,which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)dodecanamidehydrochloride (0.155 g, 83% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.31 (s,1H), δ 6.49 (s, 1H), δ 4.63 (s, 2H), δ 3.97 (s, 2H), δ 2.81 (s, 2H), δ2.51 (t, J=7.2 Hz, 2H), δ 2.14 (t, J=7.2 Hz, 2H), δ 1.76 (s, 2H), δ 1.67(s, 2H), δ 1.51 (s, 2H), δ 1.44 (s, 2H), δ 1.26 (bs, 16H), δ 0.71 (s,3H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 175.6, 159.4, 147.3, 127.6, 108.5,51.3, 48.6, 38.8, 35.8, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 28.2, 28.1,27.7, 24.8, 24.2, 23.9, 22.6, 22.5, 13.4, 13.3 ppm; HRMS (ESI) calcd forC₂₄H₄₃N₇O (M+) 445.3429, found 445.3524.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)tetradecanamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.111 g, 0.401 mmol)was reacted with N-(2-azidoethyl)tetradecanamide (0.130 g, 0.401 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-tetradecanamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.26 (s, 1H), δ 6.85 (s, 1H), δ 6.42 (s, 1H),δ 6.05 (s, 1H), δ 4.38 (s, 2H), δ 3.66 (s, 2H), δ 2.60 (s, 2H), δ 2.11(s, 2H), δ 2.08 (t, J=3.6 Hz, 2H), δ 1.41 (m, 13H), δ 1.32 (s, 2H), δ1.17 (s, 18H), δ 0.77 (t, J=6.6 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ202.9, 174.3, 149.6, 148.3, 121.9, 100.1, 84.8, 49.5, 42.3, 39.5, 36.7,32.1, 29.9, 29.8, 29.7, 29.6, 29.5, 29.5, 29.3, 28.9, 28.1, 25.9, 25.6,22.9, 14.3 ppm; HRMS (ESI) calcd for C₃₁H₅₅N₇O₃(M+) 573.4366, found573.4365, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)tetradecanamidehydrochloride (0.118 g, 87% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.51 (s,1H), δ 6.53 (s, 1H), δ 4.71 (s, 2H), δ 3.75 (s, 2H), δ 2.89 (s, 2H), δ2.54 (t, J=6.8 Hz, 2H), δ 2.17 (t, J=6.8 Hz, 2H), δ 1.80 (s, 2H), δ 1.69(s, 2H), δ 1.54 (s, 2H), δ 1.48 (s, 2H), δ 1.28 (s, 20H), 0.88 (t, J=6.8Hz, 3H) ppm; ¹³ C NMR (100 MHz, CD₃OD) δ 175.6, 161.8, 147.2, 127.6,127.4, 108.5, 52.3, 38.8, 36.6, 35.8, 31.9, 30.6, 29.7, 29.6, 29.5,29.4, 29.2, 28.0, 27.9, 27.7, 25.8, 24.1, 23.6, 23.4, 22.6, 13.4 ppm;HRMS (ESI) calcd for C₂₆H₄₇N₇O (M+) 473.3842, found 473.3834.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)palmitamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.087 g, 0.313 mmol)was reacted with N-(2-azidoethyl)palmitamide (0.102 g, 0.313 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-palmitamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.29 (s, 1H), δ 6.78 (t, J=4.5 Hz, 1H), δ 6.41(s, 1H), δ 6.19 (s, 2H), δ 4.39 (t, J=5.4 Hz, 2H), δ 3.67 (q, J=5.5, 4.8Hz, 2H), δ 2.61 (t, J=6.9 Hz, 2H), δ 2.12 (t, J=6.5 Hz, 2H), δ 2.07 (t,J=7.5 Hz, 2H), δ 1.42 (m, 13H), δ 1.42 (m, 2H), δ 1.32 (m, 22H), 0.81(t, J=5.4 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 176.8, 174.3, 173.9,149.5, 148.3, 121.9, 106.4, 85.0, 67.2, 51.1, 49.5, 39.5, 39.1, 38.1,36.8, 36.7, 32.1, 29.9, 29.8, 29.7, 29.6, 29.5, 29.3, 28.9, 28.3, 28.2,27.9, 25.9, 25.6, 22.9, 14.3 ppm; HRMS (ESI) calcd for C₃₃H₅₉N₇O₃ (M+)601.4679, found 601.4671, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)palmitamidehydrochloride (0.155 g, 92% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.59 (s,1H), δ 6.53 (s, 1H), δ 4.72 (s, 2H), δ 3.75 (s, 2H), δ 2.90 (s, 2H), δ2.54 (s, 2H), δ 2.16 (t, J=7.2 Hz, 2H), δ 1.80 (s, 2H), δ 1.69 (s, 2H),δ 1.51 (s, 4H), δ 1.28 (bs, 24H), δ 0.71 (t, J=6.3 Hz, 3H) ppm; ¹³C NMR(75 MHz, CD₃OD) δ 175.7, 147.2, 145.6, 128.4, 127.6, 108.6, 67.2, 52.7,37.4, 36.5, 35.8, 31.9, 29.7, 29.5, 29.4, 29.2, 28.0, 27.9, 27.8, 27.7,25.8, 24.1, 23.6, 23.2, 22.6 ppm; HRMS (ESI) calcd for C₂₈H₅₁N₇O (M+)501.4155, found 501.4143.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.116 g, 0.417 mmol)was reacted withN-(2-azidoethyl)-4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamide (0.145 g,0.417 mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.76 (s, 1H), δ 7.32 (s, 1H), δ 6.81 (s, 1H),δ 6.49 (s, 1H), δ 6.17 (s, 2H), δ 4.52 (s, 2H), δ 3.94 (s, 3H), δ 3.84(s, 2H), δ 2.65 (t, J=7.2 Hz, 2H), δ 2.30 (m, 2H), δ1.58 (m, 13H), δ1.35 (m, 2H); ¹³C NMR (75 MHz, CDCl₃) δ 161.2, 149.6, 148.2, 138.8,127.4, 122.2, 114.9, 111.9, 106.5, 98.2, 84.5, 49.5, 39.7, 35.9, 29.3,28.9, 28.2, 28.0, 27.7, 25.6 ppm; HRMS (ESI) calcd for C₂₃H₃₂N₈O₃(M+)626.0964, found 626.0960, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4,5-dibromo-1-methyl-1H-pyrrole-2-carboxamidehydrochloride (0.151 g, 64% yield). ¹N NMR (400 MHz, CD₃OD) δ 8.24 (s,1H), δ 6.86 (s, 1H), δ 6.56 (s, 1H), δ 4.71 (s, 2H), δ 3.81 (s, 5H),2.78 (s, 2H), δ 2.44 (t, J=7.2 Hz, 2H), δ 1.69 (s, 2H), δ 1.59 (s, 2H),δ 1.37 (s, 2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 161.4, 150.2, 159.8,159.4, 147.3, 127.6, 127.3, 114.9, 111.6, 108.4, 97.9, 51.3, 39.0, 35.2,28.3, 28.0, 27.6, 24.2, 23.8 ppm; HRMS (ESI) calcd for C₁₈H₂₄Br₂N₈O (M+)526.0439, found 526.0425.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-bromo-1H-pyrrole-2-carboxamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.104 g, 0.375 mmol)was reacted with N-(2-azidoethyl)-4-bromo-1H-pyrrole-2-carboxamide(0.131 g, 0.375 mmol) following the general click procedure to givetert-butyl2-amino-4-(5-(1-(2-(4-bromo-1H-pyrrole-2-carboxamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 11.44 (s, 1H), δ 7.84 (s, 1H), δ 7.28 (s, 1H),δ 6.84 (s, 1H), δ 6.74 (s, 1H), δ 6.46 (s, 1H), δ 4.89 (s, 2H), δ 3.82(s, 2H), δ 2.57 (s, 2H), δ 2.28 (s, 2H), δ 1.55 (m, 13H), δ 1.29 (m, 2H)ppm; ¹³C NMR (75 MHz, CDCl₃) δ 186.8, 161.4, 150.7, 149.3, 148.2, 137.6,126.3, 122.5, 122.1, 113.1, 100.4, 96.9, 85.4, 49.6, 29.1, 28.7, 28.2,27.7, 25.5 ppm; HRMS (ESI) calcd for C₂₂H₃₁BrN₈O₃(M+) 534.1703, found534.1705, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-bromo-1H-pyrrole-2-carboxamidehydrochloride (0.129 g, 73% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.42 (s,1H), δ 6.93 (s, 1H), δ 6.82 (s, 1H), δ 6.47 (s, 1H), δ 4.76 (s, 2H), δ3.87 (s, 2H), δ 2.79 (s, 2H), δ 2.45 (s, 2H), δ 1.69 (s, 2H), δ 1.60 (s,2H), δ 1.37 (s, 2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 161.4, 159.5, 159.1,147.3, 147.2, 127.6, 125.8, 122.3, 122.1, 112.8, 108.6, 108.5, 96.4,51.9, 38.9, 28.0, 27.9, 27.6, 24.1, 23.6 ppm; HRMS (ESI) calcd forC₁₇H₂₃BrN₈O (M+) 434.1178, found 434.1171.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-1H-pyrrole-2-carboxamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.097 g, 0.349 mmol)was reacted with N-(2-azidoethyl)-1H-pyrrole-2-carboxamide (0.063 g,0.349 mmol) following the general click procedure to give tert-butyl4-(5-(1-(2-(1H-carboxylate ¹H NMR (300 MHz, CDCl₃) δ 8.18 (s, 1H), δ7.36 (d, J=5.7 Hz, 2H), δ 7.24 (s, 1H), δ 6.84 (t, J=8.1 Hz, 1H), δ 6.43(s, 1H), δ 6.04 (s, 2H), 4.49 (s, 2H), δ 3.89 (s, 2H), δ 2.53 (s, 2H), δ2.09 (s, 2H), δ 1.44 (m, 13H), δ 1.24 (s, 2H) ppm; ¹³C NMR (75 MHz,CDCl₃) δ 165.9, 164.8, 164.6, 161.5, 137.5, 122.3, 111.0, 110.7, 107.5,107.1, 106.8, 85.1, 49.4, 40.5, 29.3, 28.9, 28.2, 25.5 ppm; HRMS (ESI)calcd for C₂₂H₃₂N₈O₃(M+) 456.2597, found 456.2590, which wassubsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-1H-pyrrole-2-carboxamidehydrochloride (0.129 g, 94% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.65 (s,1H), δ 7.41 (s, 2H), δ 7.17 (s, 1H), δ 6.50 (s, 1H), δ 4.74 (s, 2H), δ3.98 (s, 2H), δ 2.88 (s, 2H), δ 2.49 (s, 2H), δ 1.78 (m, 4H), δ 1.44 (s,2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 166.3, 164.5, 162.0, 161.9, 137.4,110.6, 110.3, 110.2, 108.5, 17.1, 106.8, 59.3, 52.4, 39.5, 36.5, 27.9,27.8, 27.6, 24.1, 23.5, 23.3 ppm; HRMS (ESI) calcd for C₁₇H₂₄H₈O (M+)356.2073, found 356.2080.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-tert-butylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.070 g, 0.253 mmol)was reacted with N-(2-azidoethyl)-4-tert-butylbenzamide (0.062 g, 0.253mmol) following, the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-tert-butylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.71 (d, J=7.5 Hz, 2H), δ 7.64 (t, J=5.7 Hz,1H), δ 7.36 (d, J=7.5 Hz, 2H), δ 7.27 (s, 1H), δ 6.42 (s, 1H), δ 5.99(s, 2H), δ 4.51 (t, J=5.7 Hz, 2H), δ 3.88 (q, J=5.1, 5.3 Hz, 2H), δ 2.58(t, J=7.5 Hz, 2H), δ 2.22 (t, J=7.5 Hz, 2H), δ 1.52 (m, 13H), δ 1.21 (m,11H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.2, 155.3, 150.4, 149.6, 148.3,138.9, 131.2, 127.3, 125.6, 122.2, 106.5, 84.8, 49.4, 40.2, 35.1, 31.3,31.1, 29.3, 28.9, 28.3, 28.2, 28.1, 25.6 ppm; HRMS (ESI) calcd forC₂₈H₄₁N₇O₃ (M+) 523.3271, found 523.3270, which was subsequentlydeprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-tert-butylbenzamidehydrochloride (0.105 g, 90% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.48 (s,1H), δ 7.76 (d, J=6.3 Hz, 2H), δ 7.48 (d, J=6.3 Hz, 2H), δ 6.50 (s, 1H),δ 4.84 (s, 2H), δ 3.95 (s, 2H), δ 2.85 (s, 2H), δ 2.46 (t, J=5.4 Hz,2H), δ 1.73 (s, 2H), δ 1.57 (m, 2H), δ 1.39 (s, 2H), δ 1.31 (s, 9H) ppm;¹³C NMR (100 MHz, CD₃OD) δ 169.2, 155.6, 147.3, 130.8, 129.9, 127.6,127.2, 127.1, 126.7, 125.4, 125.3, 119.5, 108.6, 108.5, 52.3, 39.4,34.6, 30.4, 27.9, 27.8, 27.6, 24.1, 23.2, 22.2 ppm; HRMS (ESI) calcd forC₂₃H₃₃N₇O (M+) 423.2747, found 423.2741.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-naphthamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.095 g, 0.344 mmol)was reacted with N-(2-azidoethyl)-2-naphthamide (0.083 g, 0.344 mmol)following the general click procedure to give tert-butyl4-(5-(1-(2-(2-naphthamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-2-amino-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 8.24 (s, 1H), δ 8.01 (s, 1H), δ 7.72 (m, 4H),δ 7.39 (m, 2H), δ 7.26 (s, 1H), δ 6.33 (s, 1H), δ 6.04 (s, 2H), δ 4.51(s, 2H), δ 3.88 (s, 2H), δ 2.48 (t, 2H), δ 2.12 (s, 2H), δ 1.47 (m,13H), δ 1.17 (s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 168.5, 150.4, 149.5,148.3, 138.6, 134.9, 132.7, 131.4, 129.2, 128.5, 128.1, 127.9, 126.8,124.0, 122.3, 106.5, 84.9, 49.4, 40.4, 29.9, 29.2, 28.9, 28.6, 28.2,27.9, 28.6, 27.9, 27.8, 25.6 ppm; HRMS (ESI) calcd for C₂₈H₃₅N₇O₃ (M+)517.2801, found 517.2792, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-naphthamidehydrochloride (0.140 g, 90% yield). ¹H NMR (300 MHz, CD₃OD) δ ppm; ¹³CNMR (75 MHz, CD₃OD) δ ppm; HRMS (ESI) calcd for C₂₃H₂₇N₇O (M+) 417.2277,found 417.2274.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-iodobenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.083 g, 0.299 mmol)was reacted with N-(2-azidoethyl)-2-iodobenzamide (0.095 g, 0.299 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(2-iodobenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.74 (d, J=7.5 Hz, 2H), δ 7.57 (t, J=4.5 Hz,1H), δ 7.36 (s, 1H), δ 7.22 (s, 2H), δ 6.97 (m, 1H), δ 6.39 (s, 1H), δ5.97 (s, 2H), δ 4.48 (t, J=5.1 Hz, 2H), δ 3.85 (m, 2H), δ 2.44 (t, J=7.5Hz, 2H), δ 2.18 (t. J=6.6 Hz, 2H), δ 1.45 (m, 13H, δ 1.18 (m, 2H) ppm;¹³C NMR (75 MHz, CDCl₃) δ 170.3, 150.4, 149.5, 148.2, 141.8, 139.9,138.7, 131.3, 128.4, 128.3, 122.3, 106.5, 92.8, 84.9, 49.2, 40.5, 29.2,28.9, 28.3, 28.2, 28.0, 25.5 ppm; HRMS (ESI) calcd for C₂₄H₃₂IN₇O₃ (M+)593.1611, found 593.1603, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2-iodobenzamidehydrochloride (0.125 g, 79% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.35 (s,1H), δ 7.88 (d, J=7.8 Hz, 1H), δ 7.45 (t, J=6.9 Hz, 1H), δ 7.34 (d,J=6.9 Hz, 1H), δ 7.15 (t, J=7.5 Hz, 1H), δ 6.47 (s, 1H), δ 4.78 (s, 2H),δ 3.99 (s, 2H), δ 2.83 (s, 2H), δ 2.44 (t, J=6.9 Hz, 2H), δ 1.76 (s,2H), δ 1.64 (s, 2H), δ 1.29 (s, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ171.6, 159.2, 147.3, 142.1, 139.8, 131.2, 128.2, 127.7, 124.4, 92.1,52.2, 40.8, 39.4, 31.2, 28.3, 28.1, 27.7, 24.1, 20.9, 15.9, 10.7 ppm;HRMS (ESI) calcd for C₁₉H₂₄IN₇O (M+) 493.1087, found 493.1085.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-heptylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.125 g, 0.449 mmol)was reacted with N-(2-azidoethyl)-4-heptylbenzamide (0.129 g, 0.449mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-heptylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (400 MHz, CDCl₃) δ 7.78 (s, 1H), δ 7.65 (d, 2H), δ 7.27 (s, 1H),δ 7.09 (d, 2H), δ 6.39 (s, 1H), δ 6.22 (s, 2H), δ 4.47 (s, 2H), δ 3.81(s, 2H), δ 3.96 (s, 4H), δ 2.20 (s, 2H), δ 2.05 (s, 2H), 1.48 (m, 12H),δ 1.17 (m, 8H), δ 0.77 (t, J=6.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ168.3, 149.6, 148.2, 147.1, 138.6, 131.5, 128.6, 127.4, 122.1, 106.4,84.8, 67.1, 49.4, 40.2, 37.9, 36.9, 31.9, 31.3, 31.1, 29.8, 28.4, 29.3,28.9, 28.3, 28.1, 28.0, 25.5, 22.8, 14.3 ppm; HRMS (ESI) calcd forC₃₁H₄₇N₇O₃(M+) 565.3704, found 656.3737, which was subsequentlydeprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-heptylbenzamidehydrochloride (0.194 g, 86% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.25 (s,1H), δ 7.71 (d, J=5.4 Hz, 2H), δ 7.24 (d, J=5.7 Hz, 2H), δ 6.45 (s, 1H),δ 4.74 (s, 2H), 3.90 (s, 2H), δ 2.63 (s, 2H), δ 2.61 (t, 2H), δ 2.41 (s,2H), δ 1.58 (m, 6H), δ 1.26 (m, 10H), δ 0.85 (t, J=4.8 Hz, 3H) ppm; ¹³CNMR (100 MHz, CD₃OD) δ 169.2, 150.2, 147.4, 131.2, 128.5, 127.6, 127.3,108.4, 51.4, 39.6, 36.5, 35.6, 31.8, 331.3, 29.1, 29.1, 28.3, 28.0,27.7, 24.1, 22.6, 13.4, 13.3 ppm; HRMS (ESI) calcd for C₂₆H₃₉N₇O (M+)465.3216, found 465.3207.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-hexylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.097 g, 0.349 mmol)was reacted with N-(2-azidoethyl)-4-hexylbenzamide (0.096 g, 0.349 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-hexylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.65 (d, J=8.1 Hz, 2H), δ 7.55 (t, J=6.7 Hz,1H), δ 7.26 (s, 1H), δ 7.09 (d, J=7.8 Hz, 2H), δ 6.39 (s, 1H), δ 6.04(s, 2H), δ 4.48 (t, J=4.8 Hz, 2H), δ 3.83 (q, J=5.6, 4.8 Hz, 2H), δ 2.56(q, J=7.5, 8.1 Hz, 4H), δ 2.24 (t, J=6.9 Hz, 2H), δ 1.50 (m, 13H), δ1.21 (m, 1H), δ 0.77 (t, J=5.7 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ168.3, 148.3, 147.3, 138.7, 131.4, 128.7, 127.4, 122.2, 106.4, 84.9,73.9, 49.5, 40.2, 36.0, 31.8, 31.3, 29.9, 29.3, 29.1, 28.9, 28.2, 28.1,28.0, 25.6, 22.8, 14.3 ppm; HRMS (ESI) calcd for C₃₀H₄₅N₇O₃ (M+)551.3584, found 551.3581, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-hexylbenzamidehydrochloride (0.164 g, 96% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.28 (s,1H), δ 7.67 (d, J=7.6 Hz, 2H), δ 7.21 (d, J=7.6 Hz, 2H), δ 6.43 (s, 1H),δ 4.72 (s, 2H), δ 3.87 (s, 2H), δ 2.74 (s, 2H), δ 2.58 (t, J=7.6 Hz,2H), δ 2.31 (t, J=6.8 Hz, 2H), δ 1.66 (s, 2H), δ 1.55 (s, 4H), δ 1.35(s, 2H), δ 1.25 (s, 6H), δ 0.66 (t, J=8.8 Hz, 3H) ppm; ¹³C NMR (100 MHz,CD₃OD) δ 169.2, 159.5, 147.4, 147.3, 131.2, 108.4, 51.2, 48.5, 48.3,48.1, 47.9, 47.7, 47.5, 47.3, 39.5, 36.5, 35.6, 31.6, 31.7, 31.2, 28.8,28.2, 27.9, 27.7, 24.1, 23.9, 22.6, 13.3, 9.9 ppm; HRMS (ESI) calcd forC₂₅H₃₇N₇O (M+) 451.3059, found 451.3058.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-butylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.123 g, 0.443 mmol)was reacted with N-(2-azidoethyl)-4-butylbenzamide (0.109 g, 0.443 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-butylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.67 (s, 1H), δ 7.67 (d, J=7.5 Hz, 2H), δ 7.29(s, 1H), δ 7.11 (d, J=7.5 Hz, 2H), δ 6.42 (s, 1H), δ 6.25 (s, 2H), δ4.48 (s, 2H), δ 3.83 (s, 2H), δ 2.56 (t, J=7.2 Hz, 4H), δ 2.21 (s, 2H),1.47 (m, 13H), δ 1.21 (m, 4H), δ 0.83 (t, J=7.2 Hz, 3H) ppm; ¹³C NMR (75MHz, CDCl₃) δ168.3, 140.6, 149.5, 148.2, 147.1, 138.4, 131.5, 128.7,127.4, 122.2, 106.4, 84.9, 49.4, 40.2, 35.7, 33.5, 29.2, 28.9, 28.3,28.1, 27.9, 25.5, 22.4, 14.1 ppm; HRMS (ESI) calcd for C₂₈H₄₁N₇O₃ (M+)523.3271, found 523.3261, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-butylbenzamidehydrochloride (0.191 g, 94% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.43 (s,1H), δ 7.69 (s, 2H), δ 7.22 (s, 2H), δ 6.44 (s, 1H), δ 4.73 (s, 2H), δ3.89 (s, 2H), δ 3.34 (s, 2H), δ 2.59 (s, 4H), δ 2.41 (s, 2H), δ 1.54 (s,4H), δ 1.29 (s, 4H), δ 0.88 (t, J=6.9 Hz, 3H) ppm; ¹³C NMR (75 MHz,CD₃OD) δ 169.2, 165.1, 160.3, 158.1, 147.4, 141.4, 131.2, 128.5, 127.7,127.3, 126.9, 92.9, 39.6, 36.3, 33.4, 30.9, 28.0, 27.7, 24.1, 22.2,13.2, 12.1, 10.9, 8.9, 6.2, 2.5 ppm; HRMS (ESI) calcd for C₂₃H₃₃N₇O (M+)423.2747, found 423.2738.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-pentylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.113 g, 0.408 mmol)was reacted withN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)biphenyl-4-carboxamidehydrochloride (0.106 g, 0.408 mmol) following the general clickprocedure to give tert-butyl2-amino-4-(5-(1-(2-(4-pentylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.75 (s, 1H), δ 7.67 (d, J=7.5 Hz, 2H), δ 7.27(s, 1H), δ 7.12 (d, J=7.8 Hz, 2H), δ 4.48 (s, 2H), δ 3.84 (s, 2H), δ2.55 (m, 4H), δ 2.22 (s, 2H), δ 1.50 (s, 13H), δ 1.23 (s, 8H), δ 0.80(t, J=5.7 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ ppm 168.3, 150.5, 149.5,147.2, 138.6, 131.5, 128.7, 127.4, 106.4, 84.8, 49.4, 40.2, 35.9, 31.6,31.0, 29.3, 28.9, 28.1, 27.9, 25.6, 22.6, 14.2; HRMS (ESI) calcd forC₂₉H₄₃N₇O₃ (M+) 537.3427, found 537.3420, which was subsequentlydeprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-pentylbenzamidehydrochloride (0.178 g, 92% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.41 (s,1H), δ 7.69 (d, J=7.5 Hz, 2H), δ 7.21 (d, J=7.2 Hz, 2H), δ 6.46 (s, 1H),δ 4.84 (s, 2H), δ 3.90 (s, 2H), δ 2.79 (s, 2H), δ 2.58 (t, J=7.8 Hz,2H), δ 2.39 (t, J=7.2 Hz, 2H), δ 1.68 (s, 2H), δ 1.55 (s, 4H), δ 1.26(s, 6H), δ 0.84 (t, J=6.6 Hz, 3H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ 169.2,159.5, 158.9, 147.5, 147.3, 131.1, 128.5, 127.6, 127.4, 108.5, 54.2,51.9, 39.5, 35.6, 31.4, 30.9, 30.6, 28.4, 27.9, 27.6, 26.9, 24.1, 23.5,22.9, 22.4, 13.3 ppm; HRMS (ESI) calcd for C₂₄H₃₅N₇O (M+) 437.2903,found 437.2892.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2,4,6-trichlorobenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.088 g, 0.318 mmol)was reacted with N-(2-azidoethyl)-2,4,6-trichlorobenzamide (0.093 g,0.318 mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(2,4,6-trichlorobenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 8.22 (s, 1H), δ 7.34 (s, 1H), δ 7.26 (s, 2H),δ 6.42 (s, 1H), δ 5.97 (s, 2H), δ 4.51 (s, 2H), δ 3.94 (s, 2H), δ 2.45(t, 2H), δ 2.20 (s, 2H), δ 1.47 (m 13H), δ 1.21 (m, 2H) ppm; ¹³C NMR (75MHz, CDCl₃) δ 164.7, 148.0, 135.7, 134.6, 132.9, 128.7, 128.1, 127.3,122.3, 84.9, 53.7, 49.3, 39.9, 31.8, 29.2, 28.9, 28.2, 25.5, 22.8, 14.3ppm; HRMS (ESI) calcd for C₂₄H₃₀Cl₃N₇O₃ (M+) 569.1476, found 569.1477,which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2,4,6-trichlorobenzamidehydrochloride (0.116 g, 72% yield). ¹H NMR (300 MHz, CD₃OD) δ 8.36 (s,1H), δ 7.45 (s, 2H), δ 6.46 (s, 1H), δ 4.77 (s, 2H), δ 3.97 (s, 2H), δ2.80 (s, 2H), δ 2.48 (t, J=6.9 Hz, 2H), δ 1.73 (s, 2H), δ 1.62 (s, 2H),δ 1.41 (s, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ 165.5, 147.3, 136.9,134.5, 132.7, 128.2, 128.0, 127.6, 108.6, 51.2, 39.0, 28.1, 27.7, 24.1,23.8 ppm; HRMS (ESI) calcd for C₁₉H₂₂Cl₃N₇O (M+) 469.0951, found469.0941.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-difluorobenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.123 g, 0.442 mmol)was reacted with N-(2-azidoethyl)-3,5-difluorobenzamide (0.100 g, 0.442mmol) following, the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(3,5-difluorobenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 8.25 (s, 1H), δ 7.39 (m, 3H), δ 6.88 (t, J=4.8Hz, 1H), δ 6.43 (s, 1H), δ 6.38 (bs, 2H), δ 4.55 (s, 2H), δ 3.93 (s,2H), δ 2.56 (t, J=5.1 Hz, 2H), δ 2.24 (s, 2H), δ 1.55 (m, 14H), δ 1.23(s, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 165.9, 164.3, 164.2, 161.9,150.3, 149.3, 148.2, 137.6, 1214, 111.0, 110.8, 107.3, 107.1, 106.8,106.6, 85.5, 49.3, 40.4, 29.9, 29.5, 29.1, 28.7, 28.2, 27.9, 27.5, 25.4ppm; HRMS (ESI) calcd for C₂₄H₃₁F₂N₇O₃(M+) 503.2456, found 503.2458,which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-difluorobenzamidehydrochloride (0.115 g, 59% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.55 (s,1H), δ 7.42 (d, J=2.0 Hz, 2H), δ 7.29 (t, J=2.40 Hz, 1H), δ 6.51 (s,1H), δ 4.84 (t, J=4.8 Hz, 2H), δ 3.96 (q, J=13.2, 4.8 Hz, 2H), δ 2.89(t, J=7.2 Hz, 2H), δ 2.49 (t, J=7.2 Hz, 2H), δ 1.79 (m, 2H), δ 1.75 (m,2H), δ 1.44 (m, 2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 164.5, 164.4, 127.6,126.9, 110.6, 110.6, 110.3, 108.5, 107.1, 106.8, 106.6, 52.5, 39.5,30.4, 27.9, 27.8, 27.6, 24.0, 23.8, 23.1 ppm; HRMS (ESI) calcd forC₁₉H₂₃F₂N₇O (M+) 403.1932, found 403.1926.

N-(2-(4-(5-(2-amino4H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)biphenyl-4-carboxamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.093 g, 0.334 mmol)was reacted with N-(2-azidoethyl)biphenyl-4-carboxamide (0.089 g, 0.334mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-biphenyl-4-ylcarboxamidoethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.91 (d, J=5.1 Hz, 3H), δ 7.57 (t, J=8.4 Hz,4H), δ 7.44 (t, J=6.9 Hz, 3H), δ 7.34 (1H), δ 4.60 (t, J=5.1 Hz, 2H), δ3.96 (q, J=5.1, 5.4 Hz, 2H), δ 2.63 (t, J=7.2 Hz, 2H), δ 2.27 (t, J=7.5Hz, 2H), δ 1.62 (m, 13H), δ 1.33 (m, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ168.0, 149.6, 148.3, 144.6, 140.1, 138.8, 132.8, 129.1, 128.2, 128.0,127.4, 127.3, 122.2, 84.9, 49.4, 40.3, 29.3, 28.9, 28.3, 28.2, 28.1,25.6 ppm; HRMS (ESI) calcd for C₃₀H₃₇N₇O₃ (M+) 543.2958, found 543.2949,which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)biphenyl-4-carboxamide hydrochloride (0.093 g, 58%yield). ¹H NMR (300 MHz, CD₃OD) δ 8.35 (s, 1H), δ 7.88 (d, J=8.1 Hz,2H), δ 7.65 (d, J=8.4 Hz, 2H), δ 7.57 (d, J=7.5 Hz, 2H), δ 7.39 (t,J=7.5 Hz, 2H), δ 7.34 (t, J=7.2 Hz, 1H), δ 6.39 (s, 1H), δ 4.81 (s, 2H),δ 3.96 (s, 2H), δ 2.78 (s, 2H), δ 2.37 (t, J=7.5 Hz, 2H), δ 1.67 (s,2H), δ 1.56 (t, 2H), δ 1.33 (s, 2H) ppm; ¹³C NMR (75 MHz, CD₃OD) δ203.6, 158.9, 160.1, 159.5, 159.1, 159.0, 158.5, 149.8, 147.2, 144.6,132.4, 128.9, 127.9, 127.6, 126.9, 126.4, 108.4, 51.7, 39.5, 27.9, 27.6,24.0, 23.5, 7.2 ppm; HRMS (ESI) calcd for C₂₅H₂₉N₇O (M+) 443.2434, found443.2423.

N-(2-4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-octylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.078 g, 0.282 mmol)was reacted with N-(2-azidoethyl)-4-octylbenzamide (0.085 g, 0.282 mmol)following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-octylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.64 (s, 2H), δ 7.47 (s, 1H), δ 7.21 (s, 1H),δ 7.09 (s, 2H), δ 6.47 (bs, 3H), δ 4.48 (s, 2H), δ 3.84 (s, 2H), δ 2.53(s, 4H), δ 2.28 (t, J=15.9 Hz, 2H), δ 1.51 (bs, 6H), δ 1.18 (bs, 10H),0.77 (t, J=6.6 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ 180.7, 180.2,168.3, 147.4, 142.4, 139.2, 131.4, 128.8, 127.4, 107.4, 49.6, 40.2,36.1, 32.1, 31.4, 29.9, 29.6, 29.5, 28.8, 28.2, 28.1, 25.4, 22.9, 14.3ppm; HRMS (ESI) calcd for C₃₂H₄₉N₇O₃ (M+) 579.3896, found 579.3890,which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-octylbenzamidehydrochloride (0.097 g, 67% yield). ¹H NMR (400 MHz, CD₃OD) δ 7.65 (s,2H), δ 7.23 (s, 3H), δ 6.45 (s, 1H), δ 3.97 (s, 4H), δ 2.60 (s, 4H), δ2.47 (s, 2H), δ 1.57 (m, 6H), δ 1.27 (bm, 12H), δ 0.83 (t, J=6.4 Hz, 3H)ppm; ¹³C NMR (100 MHz, CD₃OD) δ 183.5, 172.0, 169.3, 161.8, 153.9,147.4, 131.2, 128.5, 127.7, 127.3, 119.1, 108.8, 104.7, 94.6, 63.4,38.7, 35.6, 31.8, 31.3, 29.3, 29.2, 29.1, 28.1, 27.7, 27.1, 24.2, 22.5,13.3, 12.6 ppm; HRMS (ESI) calcd for C₂₇H₄₁N₇O (M+) 479.3372, found479.3378.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-nonylbenzamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (g, mmol) was reactedwith (g, mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(4-nonylbenzamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 7.70 (d, J=7.2 Hz, 2H), δ 7.29 (s, 1H), δ 7.27(t, J=8.7 Hz, 1H), δ 7.16 (d, J=7.2 Hz, 2H), δ 4.53 (s, 2H), δ 3.91 (s,2H), δ 2.61 (m, 4H), δ 2.41 (m, 1H), δ 2.14 (s, 1H), δ 1.56 (bs, 15H), δ1.23 (bs, 14H), δ 0.83 (t, J=6.6 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃) δ188.1, 169.7, 168.3, 164.4, 148.0, 147.4, 131.4, 128.8, 127.4, 122.2,51.6, 49.5, 40.2, 36.0, 32.1, 31.4, 29.7, 29.6, 29.5, 29.4, 29.3, 28.2,25.6, 22.9, 14.3 ppm; HRMS (ESI) calcd for C₃₃H₅₁N₇O₃ (M+) 593.4053,found 593.4049, which was subsequently deprotected to giveN-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-nonylbenzamidehydrochloride (0.183 g, 74% yield). ¹H NMR (400 MHz, CD₃OD) δ 8.66 (s,1H), δ 7.69 (s, 2H), δ 7.25 (s, 2H), δ 6.54 (s, 1H), δ 4.81 (s, 2H), δ3.62 (s, 2H), δ 2.85 (s, 2H), δ 2.63 (s, 2H), δ 2.46 (s, 2H), δ 1.75 (s,2H), δ 1.39 (s, 4H), δ 1.29 (m, 14H), δ 0.88 (s, 3H) ppm; ¹³C NMR (100MHz, CD₃OD) δ 205.0, 169.2, 147.5, 147.3, 131.2, 128.5, 127.3, 108.9,108.6, 96.0, 52.4, 51.6, 39.3, 38.9, 35.6, 31.9, 31.3, 30.6, 29.5, 29.4,29.3, 29.2, 28.1, 27.9, 27.7, 24.1, 23.6, 22.6, 13.4 ppm; HRMS (ESI)calcd for C₂₈H₄₃N₇O (M+) 493.3529, found 493.3522.

N-(2-(4-(5-(2-amino-1H-imidazol-4-yl)pentyl)-1H-1,2,3-triazol-1-yl)ethyl)-2′,4′-difluoro-3-hydroxybiphenyl-4-carboxamidehydrochloride: tert-butyl2-amino-4-(hept-6-ynyl)-1H-imidazole-1-carboxylate (0.085 g, 0.306 mmol)was reacted withN-(2-azidoethyl)-2′,4′-difluoro-3-hydroxybiphenyl-4-carboxamide (0.097g, 0.306 mmol) following the general click procedure to give tert-butyl2-amino-4-(5-(1-(2-(2′,4′-difluoro-3-hydroxybiphenyl-4-ylcarboxamido)ethyl)-1H-1,2,3-triazol-4-yl)pentyl)-1H-imidazole-1-carboxylate¹H NMR (300 MHz, CDCl₃) δ 8.54 (S, 1H), δ 7.83 (s, 1H), δ 7.37 (d, J=7.2Hz, 1H), δ 7.28 (s, 1H), δ 7.18 (s, 1H), δ 6.89 (d, J=7.8 Hz, 1H), δ6.72 (s, 2H), δ 6.39 (s, 1H), δ 4.57 (s, 2H), δ 3.81 (s, 2H), δ 3.34 (s,1H), δ 2.47 (s, 2H), δ 2.07 (s, 2H), δ 1.49 (m, 13H), δ 1.17 (s, 2H)ppm; ¹³C NMR (75 MHz, CDCl₃) δ 169.5, 163.7, 161.3, 160.5, 159.9, 150.5,149.2, 148.2, 137.1, 136.3, 134.5, 131.4, 12.8, 126.8, 124.4, 122.3,117.9, 116.1, 111.9, 111.6, 106.7, 104.8, 104.4, 104.1, 85.8, 50.5,49.4, 46.6, 50.0, 37.9, 29.9, 28.9, 28.5, 28.3, 28.1, 27.4, 25.3, 25.0ppm; HRMS (ESI) calcd for C₃₀H₃₅F₂N₄O₄(M+) 595.2729, found 595.2717,which was subsequently deprotected to give (0.137 g, 84% yield).

¹H NMR (400 MHz, CD₃OD) δ 8.60 (s, 1H), δ 7.89 (s, 1H), δ 7.52 (s, 2H),δ 6.97 (t, J=6.3 Hz, 3H), δ 6.45 (s, 1H), δ 4.81 (s, 2H), δ 2.78 (s,2H), δ 2.42 (s, 2H), δ 1.72 (s, 2H), δ 1.61 (d, J=7.8 Hz, 2H), δ 1.38(s, 2H) ppm; ¹³C NMR (100 MHz, CD₃OD) δ 172.9, 169.8, 161.6, 159.5,147.2, 134.4, 131.7, 128.4, 127.6, 126.0, 117.5, 115.6, 111.7, 111.5,108.5, 104.2, 104.0, 103.7, 94.6, 51.9, 39.0, 27.9, 27.6, 26.8, 24.1,23.8 ppm; HRMS (ESI) calcd for C₂₅H₂₇F₂N₇O₂(M+) 459.2194, found459.2190.

Procedure to Determine the Inhibitory Effect of Test Compounds on C.albicans, C. neoformans and a mixed S. epidermidis/C. albicans BiofilmFormation: Inhibition assays were performed by taking an overnightculture of yeast or yeast/bacteria strain and subculturing it at anOD₆₀₀ of 0.05 into YPD (Yeast extract, peptone and dextrose (BD 242820))media for the yeast alone or tryptic soy broth for the S. epidermidis/C.albicans. Stock solutions of predetermined concentrations of the testcompound were then made in the necessary media. These stock solutionswere aliquoted (100 μL) into the wells of the 96-well PVC microtiterplate. Sample plates were then wrapped in GLAD Press n' Seal® followedby an incubation under stationary conditions for 24 h at 37° C. Afterincubation, the media was discarded from the wells and the plates werewashed thoroughly with water. Plates were then stained with 100 μL of0.1% solution of crystal violet (CV) and then incubated at ambienttemperature for 30 min. Plates were washed with water again and theremaining stain was solubilized with 200 μL of 95% ethanol. A sample of125 μL of solubilized CV stain from each well was transferred to thecorresponding wells of a polystyrene microtiter dish. Biofilm inhibitionwas quantitated by measuring the OD₅₄₀ of each well in which a negativecontrol lane wherein no biofilm was formed served as a background andwas subtracted out.

Procedure to Determine the Dispersal Effect of Test Compounds on C.albicans and C. neoformans Preformed Biofilms: Dispersion assays wereperformed by taking an overnight culture of bacterial strain andsubculturing, it at an OD₆₀₀ of 0.01 into Yeast extract, peptone anddextrose (BD 242820) media. The resulting bacterial suspension wasaliquoted (100 μL) into the wells of a 96-well PVC microtiter plate.Plates were then wrapped in GLAD Press n' Seal® followed by anincubation under stationary conditions at ambient temperature toestablish the biofilms. After 24 h, the media was discarded from thewells and the plates were washed thoroughly with water. Stock solutionsof predetermined concentrations of the test compound were then made inthe necessary media. These stock solutions were aliquoted (100 μL) intothe wells of the 96-well PVC microtiter plate with the establishedbiofilms. Media alone was added to a subset of the wells to serve as acontrol. Sample Plates were then incubated for 24 h at 37° C. Afterincubation, the media was discarded from the wells and the plates werewashed thoroughly with water. Plates were then stained with 100 μL of0.1% solution of crystal violet (CV) and then incubated at ambienttemperature for 30 min. Plates were washed with water again and theremaining stain was solubilized with 200 μL of 95% ethanol. A sample of125 μL of solubilized CV stain from each well was transferred to thecorresponding wells of a polystyrene microtiter dish. Biofilm dispersionwas quantitated by measuring the OD₅₄₀ of each well in which a negativecontrol lane wherein no biofilm was formed served as a background andwas subtracted out.

The foregoing is illustrative of the present invention, and is not to beconstrued as limiting thereof. The invention is defined by the followingclaims, with equivalents of the claims to be included therein.

1. A method of preventing, removing or inhibiting microbial biofilmformation or microbial infection in a plant or plant part thereof,comprising applying to said plant or plant part a treatment effectiveamount of a compound of Formula (II)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u) andR^(v) is present or absent (depending upon chain saturation), and areeach independently H or alkyl; R⁶ is independently selected from thegroup consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide, wherein R⁶ is optionally substitutedwith one, two, three or four substituents independently selected from:halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide; n=0 to 10; and m=0 to 20; or an agriculturally acceptable saltthereof; or a compound of Formula (IV)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u), R^(v),R^(z) and R^(w) is present or absent (depending upon chain saturation),and is each independently H or alkyl; n=0 to 10; m=0 to 20; and p=0 to20 or an agriculturally acceptable salt thereof.
 2. The method of claim1, wherein said plant is a fruit crop plant or a vegetable crop plant.3-20. (canceled)
 21. The method of claim 1, wherein said microbialbiofilm formation or microbial infection is caused by a fungi.
 22. Themethod of claim 1, wherein said compound is applied to said plant in anamount effective to treat or control a fungal disease selected from thegroup consisting of rots, leaf molds, blights, wilts, damping-off, spot,root rot, stem rot, mildew, brown spot, gummosis, melanose, post-bloomfruit drop, scab, alternaria, canker, flyspeck, fruit blotch, dieback,downy mildews, ear rots, anthracnose bunts, smut, rust, eyespot andpecky rice. 23-34. (canceled)
 35. An agricultural compositioncomprising: (a) an agriculturally acceptable carrier; and (b) anantimicrobial or biofilm preventing, removing or inhibiting a compoundof Formula (II)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u) andR^(v) is present or absent (depending upon chain saturation), and areeach independently H or alkyl; R⁶ is independently selected from thegroup consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide, wherein R⁶ is optionally substitutedwith one, two, three or four substituents independently selected from:halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide; n=0 to 10; and m=0 to 20; or an agriculturally acceptable saltthereof; or a compound of Formula (IV)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u), R^(v),R^(z) and R^(w) is present or absent (depending upon chain saturation),and is each independently H or alkyl; n=0 to 10; m=0 to 20; and p=0 to20 or an agriculturally acceptable salt thereof.
 36. The composition ofclaim 35, further comprising a microbicide.
 37. The composition of claim36, wherein said microbicide comprises copper.
 38. (canceled)
 39. Thecomposition of claim 35, further comprising an antibiotic.
 40. Thecomposition of claim 35, further comprising a bacteriophage.
 41. Thecomposition of claim 35, further comprising a plant defense activator.42. The composition of claim 35, wherein said carrier is an aqueouscarrier or a solid particulate carrier.
 43. (canceled)
 44. The method ofclaim 1, wherein said compound is a compound of Formula (II)(a)(5)(D):

or an agriculturally acceptable salt thereof.
 45. The composition ofclaim 35, wherein said compound is a compound of Formula (II)(a)(5)(D):

or an agriculturally acceptable salt thereof.
 46. A method of enhancingthe effects of a microbicide comprising applying a compound of Formula(II)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u) andR^(v) is present or absent (depending upon chain saturation), and areeach independently H or alkyl; R⁶ is independently selected from thegroup consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide, wherein R⁶ is optionally substitutedwith one, two, three or four substituents independently selected from:halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide; n=0 to 10; and m=0 to 20; or an agriculturally acceptable saltthereof; or a compound of Formula (IV)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u), R^(v),R^(z) and R^(w) is present or absent (depending upon chain saturation),and is each independently H or alkyl; n=0 to 10; m=0 to 20; and p=0 to20 or an agriculturally acceptable salt thereof; in combination withsaid microbicide.
 47. The method of claim 46, wherein said microbicidecomprises copper.
 48. (canceled)
 49. The method of claim 46, whereinsaid microbicide is an antibiotic or a bacteriophage. 50-51. (canceled)52. The method of claim 46, wherein said active compound is a compoundof Formula (II)(a)(5)(D):

or an agriculturally acceptable salt thereof.
 53. A method of enhancingthe effects of a plant defense activator comprising applying a compoundof Formula (II)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u) andR^(v) is present or absent (depending upon chain saturation), and areeach independently H or alkyl; R⁶ is independently selected from thegroup consisting of: H, hydroxy, acyl, alkyl, alkenyl, alkynyl,cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol,sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acidsidechain, amino acid and peptide, wherein R⁶ is optionally substitutedwith one, two, three or four substituents independently selected from:halo, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo,aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo,oxy, nitro, carbonyl, carboxy, amino acid sidechain, amino acid andpeptide; n=0 to 10; and m=0 to 20; or an agriculturally acceptable saltthereof; or a compound of Formula (IV)(a):

wherein: R^(1a) and R^(1b) are each H; R², R³, R⁵ and are eachindependently H or alkyl; each occurrence of R^(x), R^(y), R^(u), R^(v),R^(z) and R^(w) is present or absent (depending upon chain saturation),and is each independently H or alkyl; n=0 to 10; m=0 to 20; and p=0 to20 or an agriculturally acceptable salt thereof; in combination withsaid plant defense activator. 54-55. (canceled)
 56. The method of claim53, wherein said active compound is a compound of Formula (II)(a)(5)(D):

or an agriculturally acceptable salt thereof.